Browsing by Subject "Lung cancer"

Now showing 1 - 17 of 17
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    An immunohistochemical analysis of antioxidant and glutathione S-transferase enzyme levels in normal and neoplastic human lung
    (Murcia : F. Hernández, 1996) Coursin, D.B.; Cihla, H.P.; Sempf, J.M.; Oberley, T.D.; Oberley, L.W.
    Samples of normal human lung and six major types of human lung carcinomas were immunostained for antioxidant enzymes (manganese and copper, zinc superoxide dismutases, catalase, and glutathione peroxidase) and six isoenzymes of glutathione Stransferase staining was generally low in tumor cells compared with the high level of staining noted in respiratory epithelium. A notable exception was heterogeneity in immunostaining for manganese superoxide dismutase in lung adenocarcinoma, which showed both positive and negative cells in the same tumor. Tumor stromal cells (fibroblast-appearing cells) often showed strong immunostaining for manganese superoxide dismutase, while stromal cells were negative for other antioxidant and glutathione S-transferase enzymes. None of the carcinomas studied had significant levels of catalase or glutathione peroxidase; this finding has potential clinical relevance since it indicates that these tumors cannot detoxify hydrogen peroxide. The low levels of antioxidant and glutathione S-transferase enzymes in tumor cells is consistent with the hypothesis that these enzymes are markers of cell differentiation.
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    Beneficios del ejercicio y/o actividad física en los cinco tipos de cáncer con mayor incidencia y mortalidad a nivel mundial: Una revisión narrativa
    (Universidad de Murcia, Servicio de Publicaciones, 2023) Fuentes-Nuñez, Javier; Olivares-Gómez, Carelia; Farías-Valenzuela, Claudio; Poblete-Aro, Carlos; Alvarez-Arangua, Sebastián; Ferrero-Hernández, Paloma
    Esta revisión tiene como objetivo declarar los beneficios del ejercicio físico y/o la actividad física en los cinco tipos de cáncer con mayor tasa mortalidad en el mundo. Se realizó una búsqueda en las bases de datos: Pubmed, Cochrane, Scopus, Web of Science, Scielo (Latinoamérica) y Medline. Los términos usados para la búsqueda fueron: “cáncer de pulmón”, “cáncer de hígado”, “cáncer de mama”, “cáncer de estómago”, “cáncer de colon”, “ejercicio físico”, “actividad física”, “ejercicio de resistencia” y “ejercicio aeróbico”. El ejercicio físico y la actividad física han demostrado beneficios tanto en variables morfológicas, metabólicas y psicológicas, teniendo un impacto positivo en el aumento de la funcionalidad, esperanza de vida y calidad de vida en pacientes con cáncer. El ejercicio aeróbico demostró mayores beneficios en el consumo de oxígeno, además de una alta adherencia, mientras que el entrenamiento de fuerza en una mayor capacidad específicamente en los miembros inferiores.
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    Cell cycle alterations and lung cancer
    (Murcia : F. Hernández, 2006) Vincenzi, B.; Schiavon, G.; Silletta, M.; Santini, D.; Perrone, G.M.; Di Marino, M.; Angeletti, S.; Baldi, A.; Tonini, G.
    It is now widely accepted that human carcinogenesis is a multi-step process and phenotypic changes during cancer progression reflect the sequential accumulation of genetic alterations in cells. The recent progress of scientific research has notably increased knowledge about biological events involved in lung cancer pathogenesis and progression, thanks to the use of molecular biology and immunohistochemistry techniques. Lots of the genetic alteration found in small cells lung cancer (SCLC) and in not small cells lung cancer (NSCLC) concern the expression of cell cycle genes, actually recognized as onco-suppressor genes and the lack of equilibrium between oncogenes and oncosuppressor genes. The present review of literature widely describes the cell cycle control, the lung cancer molecular pathogenesis, the catalog of known genetic alterations and the recent advances in global expression profiles in lung tumors, on the basis of the various hystological types too. Such data suggest the potential use of this knowledges in clinical practice both as prognostic factors and innovative therapeutic possibilities and they impose the necessity of new studies about cell cycle control and lung carcinogenesis.
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    Circ_0000520 interacts with miR-512-5p to upregulate KIAA0100 to promote malignant behaviors in lung cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wang, Linxuan; Liu, Yuan; Wu, Xiaochi; Liu, Yuan; Gu, Wenchao
    Background. CircRNAs function as pivotal molecules to regulate the malignant development of lung cancer. This study was designed to research the functional role and how it acted in lung cancer progression. Methods. Circ_0000520, microRNA-512-5p (miR512-5p) and Breast cancer-overexpressed gene 1 (KIAA0100) levels were measured through reverse transcription-quantitative polymerase chain reaction assay. Cell Counting Kit-8 assay and EdU assay were used to examine cell proliferation. Cell cycle and apoptosis were evaluated via flow cytometry. The protein levels were determined using western blot. Cell migration and invasion were assessed by wound healing assay and transwell assay. The circ_0000520 function in vivo was explored by tumor xenograft assay. The molecular interaction was analyzed via Dual-luciferase reporter assay. Results. Circ_0000520 was obviously upregulated in lung cancer tissues and cells. Silence of circ_0000520 inhibited proliferation, cell cycle progression, migration, invasion and angiogenesis but promoted cell apoptosis. Circ_0000520 downregulation reduced tumor growth of lung cancer in vivo. Circ_0000520 served as a miR-512- 5p sponge. The oncogenic function of circ_0000520 was partly achieved by sponging miR-512-5p in lung cancer. KIAA0100 was a target of miR-512-5p and miR-512-5p inhibited the malignant behaviors of lung cancer cells via downregulating KIAA0100. Circ_0000520 targeted miR-512-5p to regulate the level of KIAA0100. Conclusion. All these data demonstrated that circ_0000520 was able to drive the progression of lung cancer via the mediation of miR-512-5p/KIAA0100 axis. Circ_0000520 might be a potential biomarker for lung cancer.
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    Down-regulated REIC expression in lung carcinogenesis: a molecular target for gene therapy
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Yang, Lei; Zhao, Shuang; Xia, Pu; Zheng, Hua Chuan
    REIC (Reduced Expression in Immortalized Cells) gene is down-regulated in immortalized cells, compared with the normal parental counterparts. Its encoding protein could inhibit colony formation, tumor growth, and induce apoptosis. To investigate the roles of REIC expression in lung cancer, we examined REIC expression in lung cancer cells and tissues by RT-PCR or Western blot, and observed the effects of both recombinant REIC exposure and REIC overexpression on the aggressive phenotypes of lung cancer cells. It was found that the demethylation of REIC promoter by 5- Aza-dC could reserve its mRNA expression in lung cancer cells (P<0.05). There was a lower REIC mRNA expression in lung cancer than that in matched normal tissue (P<0.05). Recombinant REIC treatment enhanced the proliferation of lung cancer cells (P<0.05), but versa for REIC overexpression (P<0.05). Both recombinant REIC treatment and REIC overexpression induced apoptosis, and inhibited the migration and invasion of SQ-5 and KJ cells (P<0.05). Immunohistochemically, there was a positive correlation between REIC and Caspase-3 expression in lung cancer (P<0.05). According to Kaplan-Meier plotter, REIC mRNA overexpression was found to positively correlate with overall, progression-free and post- progression survival rates of lung cancer patients (P<0.05), even stratified by sex, histological subtyping, grading, TNM staging, chemotherapy, radiotherapy, or smoking. These findings suggested that down-regulated REIC expression might be involved in lung carcinogenesis due to its promoter methylation. Both recombinant REIC exposure and REIC overexpression might reverse the aggressive phenotypes of lung cancer cells. REIC may be employed as a potential target of gene therapy for lung cancer.
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    Expression of AGR2 in non small cell lung cancer
    (Murcia : F. Hernández, 2007) Fritzsche, F.R.; Dahl, E.; Dankof, A.; Burkhardt, M.; Pahl, S.; Petersen, I.; Dietel, Manfred; Kristiansen, Gitte
    We aimed to evaluate immunohistochemically the expression of the human Anterior Gradient-2 (AGR2), a gene which has recently been proposed as an oncogene for lung carcinoma development, in non small cell lung cancer and to correlate the findings to clinico-pathological data including patient survival. 95 cases of NSCLC were immunostained using a polyclonal AGR2 antibody and statistical analyses were applied to test for prognostic and diagnostic associations. AGR2 was expressed in 66.3% of cases, preferentially adenocarcinomas. There were no relevant associations with clinico-pathological paramaters. A prognostic value of AGR2 could not be demonstrated neither in multivariate nor in univariate analyses. Interestingly, this is the first study to demonstrate AGR2 expression in squamous cell carcinomas. Although a prognostic value of AGR2 seems unlikely further studies are warranted to investigate the biological role of AGR2 in NSCLC and its differential expression according to histology.
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    Expression of tropomyosins in lung cancer - a potential role in carcinogenesis and its utility in a histopathological diagnosis
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Okudela, Koji; Mitsui, Hideaki; Woo, Tetsukan; Kojima, Yoko; Matsumura, Mai; Arai, Hiromasa; Suzuki, Takehisa; Umeda, Shigeaki; Saito, Yuichi; Tajiri, Michihiko; Masuda, Munetaka; Kameda, Yoichi; Ohashi, Kenichi
    We herein analyzed the relationships between tropomyosin protein expression levels and clinicopathological factors in order to determine the significance of tropomyosins in lung cancers. Although neoplastic cells expressed different isoforms of tropomyosin, overall expression levels were lower than those in bronchial and alveolar epithelial cells. In adenocarcinomas, tropomyosin levels were markedly reduced in poorly differentiated or solid subtype carcinomas, suggesting that a loss in the expression of tropomyosins is involved in the progression of lung adenocarcinomas. The potential utility of the immunohistochemical expression of tropomyosins for a histopathological diagnosis was also investigated. The sensitivity and specificity of a loss in the expression of tropomyosins were 100% and 50%, respectively, which were superior to those for the strong expression of p53 (sensitivity 100% and specificity 44%), a conventional biomarker. An immunohistochemical examination of tropomyosins may assist in the histopathological detection of lung cancer cells in small biopsy specimens.
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    GASC1 expression in lung carcinoma is associated with smoking and prognosis of squamous cell carcinoma
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Uimonen, Katri; Merikallio, Heta; Pääkkö, Paavo; Harju, Terttu; Mannermaa, Arto; Palvimo, Jorma; Kosma, Veli-Matti; Soini, Ylermi
    GASC1 (gene amplified in squamous cell carcinoma 1) encodes a nuclear protein that epigenetically catalyses the lysine demethylation of histones. We investigated the expression of GASC1 in different histological subtypes of lung cancer (n=289). Percentage value of GASC1 immunohistochemical expression was evaluated separately in the nuclei and cytoplasms of epithelial cancer cells. The results were compared with clinicopathologic factors and the smoking history of the patients. In lung tumor cells, 38% of nuclei and 54% of the cytoplasms stained positive for GASC1. Adenocarcinomas expressed more GASC1 nuclear (p=0.00011) and cytoplasmic (p=0.00074) positivity than squamous cell carcinoma. Smokers displayed less nuclear and cytoplasmic GASC1 expression than non-smokers (p=0.028 and p=0.036, respectively). Similarly, patients with more cytoplasmic positive staining had fewer pack years (p=0.043). Nuclear GASC1 expression had an impairing effect on survival when all histological lung cancer types were analysed together (p=0.039) and separately in squamous cell lung carcinoma (p=0.016). The results reveal that GASC1 expression is higher in adenocarcinoma than squamous cell carcinoma. Smoking decreases GASC1 expression in tumor cells, indicating that tobacco smoke may influence the methylation of histone 3 lysine residues in lung cancer. Nonetheless, nuclear GASC1 predicts a poor prognosis, especially in squamous cell carcinoma.
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    Histopathological effect of pterostilbene as chemoprevention in N-nitroso-tri-chloroethylurea (NTCU)-induced lung squamous cell carcinoma (SCC) mouse model
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Surien, Omchit; Ghazali, Ahmad Rohi; Masre, Siti Fathiah
    ackground. Lung cancer is the leading cause of cancer-related deaths, and squamous cell carcinoma (SCC) is one of the most common types of lung cancer. Chemoprevention of lung cancer has gained increasing popularity as an alternative to treatment in reducing the burden of lung cancer. Pterostilbene (PS) may be developed as a chemopreventive agent due to its pharmacological activities, such as anti-proliferative, anti-inflammatory and antioxidant properties. This study aimed to investigate the effect of PS on the development of lung SCC in the mouse model. Methods. A total of 24 seven-week-old female Balb/C mice were randomly categorised into four groups, including two control groups comprising the N-nitroso-trischloroethylurea (NTCU)-induced lung SCC and vehicle control (VC) groups and two treatment groups comprising the 10 mg/kg PS (PS10) and 50 mg/kg PS (PS50) groups. All lung organs were harvested at week 26 for histopathological analysis. Results. All PS treatment groups showed chemopreventive activity by inhibiting the progression of lung SCC formation with PS10, resulting in mild hyperplasia, and PS50 was completely reversed in the normal bronchial epithelium layer compared with the VC group. PS treatment also reduced the expression of cytokeratin 5/6 in the bronchial epithelium layer. Both PS10 and PS50 significantly reduced the epithelium thickness compared to the NTCU group (p<0.05). PS is a potential chemopreventive agent against lung SCC growth by suppressing the progression of pre-malignant lesions and reducing the thickness of the bronchial epithelium. Conclusions. The underlying molecular mechanisms of PS in lung SCC should be further studied
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    Increased expression of matrix metalloproteinase-2 -MMP-2- predicts tumour recurrence and unfavourable outcome in non-small cell lung cancer
    (Murcia : F. Hernández, 2008) Leinonen, Tero; Pirinen, Risto; Böhm, Jan; Johansson, Risto; Kosma, Veli-Matti
    The purpose of this study was to analyse the expression of matrix metalloproteinase-2 (MMP-2) and its extracellular matrix metalloproteinase inducer (EMMPRIN) in non-small cell lung cancer (NSCLC), and to evaluate their significance to predict tumour behaviour. The study consists of 212 patients treated by the resection of the tumour. Tumour samples were stained immunohistochemically, and the expression of MMP-2 and EMMPRIN was evaluated both in tumour cells and in peritumoural stromal tissue. The results were compared with clinicopathological factors and survival of the patients. High expression of MMP-2 in tumour cells was found in 83 out of 191 cases (44%). Adenocarcinomas showed more often high expression of MMP-2 as compared with squamous cell or large cell carcinomas (p=0.001). High cancer cell associated MMP-2 expression was associated with increased tumour recurrence (p=0.001). Tumour stroma showed positive staining in 162 (98%) cases and was considered highly stained in 120 (72%) cases. The high stromal MMP-2 expression was noticed more often among large cell carcinomas as compared with other histological types (p=0.007). High cancer cell associated EMMPRIN expression was found in 115 (61%) cases and was associated only with high MMP-2 expression in tumour cells (p=0.006). In overall survival (OS) and disease free survival (DFS) analyses, type of tumour (p=0.001 and p=0.0004), advanced stage (p=0.001 and p=0.013) and high MMP-2 expression in tumour cells (p=0.018 and p=0.001) were associated with poor survival. Also, high stromal MMP-2 expression was related to poor outcome in both OS and DFS analyses (p=0.010 and 0.045, respectively). In multivariate analysis, stromal MMP-2 expression retained its prognostic value to predict OS and DFS (p=0.028 and p=0.039, respectively), together with tumour type and stage (p=0.017, p=0.001 and p=0.021, p=0.008, respectively). The present study shows the significant prognostic value of MMP-2 in NSCLC suggesting that the use of MMP-2 is valuable in determining the patients with more aggressive disease.
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    Long noncoding RNAs in respiratory diseases
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Zhang, Jiaxiang; Zhu, Yong; Wang, Ruilan
    Recently developed RNA microarrays and high-throughput sequencing techniques have demonstrated that long non-coding RNAs (lncRNAs) play important roles in a wide range of biological processes. Emerging evidence has confirmed the relevance of lncRNAs to diverse types of human disease, including cancer and cardiovascular disease. In this review, we discuss the important functions of lncRNAs in respiratory diseases. Because the reviewed studies have mainly focused on non-small cell lung cancer, future work will need to extend the studies into other respiratory diseases. From a clinical perspective, targeting lncRNAs as a novel therapeutic strategy in respiratory diseases will require further study to further clarify their biological functions.
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    Molecular characterization of small peripheral lung tumors based on the analysis of fine needle aspirates
    (Murcia : F. Hernández, 2008) Zudaire, I.; Lozano, M.D.; Vazquez, M.F.; Pajares, M.J.; Agorreta, J.; Pio, R.; Zulueta, J.J.; Yankelevitz, D.F.; Henschke, C.I.; Montuenga, L.M.
    The computed tomography (CT)-based early lung cancer diagnostic technologies allow the detection of very small stage I lung tumors. As part of these screening protocols any suspicious nodule has to be diagnosed morphologically, which requires CT-guided Fine Needle Aspiration, open biopsy or surgery. Fine Needle Aspiration (FNA) cytology is a well-recognised method for a rapid and accurate diagnosis of small lung tumors. Molecular analysis of the FNA specimens could complement cytology diagnosis by the characterization of the biological traits at the preoperative stage. In this study, we aimed to characterize the biological profile of 33 paraffin-embedded transthoracic FNA samples obtained from three groups of lung cancer patients: two groups of small early-detected lung adenocarcinomas (radiologically subsolid and solid nodules) and a third group of small metastatic adenocarcinomas. Genetic analysis was performed by fluorescence in situ hybridization using the four-color LAVysion probe. p53 and Ki-67 protein expression was also evaluated by immunocytochemistry. The samples showed gains for all targets analyzed; two cases had EGFR gene amplification and two cases had MYC amplification. There were no significant differences in the percentage of genetically malignant cells and the expression of Ki- 67 among the three groups. However, p53 accumulation was significantly higher in the metastatic group compared to the subsolid early-detected group (P = 0.001). In conclusion, molecular analysis of FNA specimens may provide useful information at preoperative stages. In our series, a good prognostic profile in subsolid early detected adenocarcinomas is suggested.
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    Prognostic index expression of cyclin-D1, cerbB-2 and VEGF metastases vs corresponding primary cancers and metastatic vs non-metastatic adenocarcinomas
    (Murcia : F. Hernández, 2008) Roger Parra, Edwin; Young Park, Ji; Midori Saito, Dalva; Yae Takagaki, Teresa; Ribeiro Rodrigues, Olavo; Capelozzi, Vera Luiza
    The prognostic relevance of different molecular markers in lung cancer is a crucial issue still worth investigating, and the specimens collected and analyzed represent a valuable source of material. Cyclin- D1, c-erbB-2 and vascular endothelial growth factor (VEGF) have shown to be promising as prognosticators in human cancer. In this study, we sought to examine the importance of Cyclin-D1, c-erbB-2 and VEGF, and to study the quantitative relationship among these factors and disease progression in metastases vs corresponding primary cancer, and metastatic vs non metastatic cancers. Material and Methods: We used immunohistochemistry and morphometric analysis to evaluate the amount of tumour staining for Cyclin-D1, cerbB- 2 and VEGF in 52 patients with surgically excised ademocarcinoma of the lung, and the outcome for our study was survival time until death from hematogenic metastases. Results: Metastasis presented lower c-erbB-2 expression than corresponding primary cancers (p=0.02). Cyclin-D1 and VEGF expression were also lower in metastases than in corresponding primary cancers, but this difference did not achieve statistical significance. Non-metastatic cancers also presented significantly lower Cyclin-D1 and c-erbB-2 expression than metastatic cancers (p<0.01 and p<0.01, respectively). Equally significant was the difference between higher cerbB- 2 expression by metastatic cancers compared to non-metastatic cancers (p=0.02). Considering survival in Kaplan-Maier analysis, Cyclin-D1 (p=0.04), c-erbB-2 (p=0.04) and VEGF (p<0.01) were important predictors of survival in metastatic cancers.
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    Stigmasterol inhibits the progression of lung cancer by regulating retinoic acid-related orphan receptor C
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Dong, Yuan; Chen, Congcong; Chen, Chen; Zhang, Chunxia; Zhang, Lei; Zhang, Yan; Li, Yongliang; Dong, Zhiqiang
    Objective. This study aims to investigate the role of stigmasterol in lung cancer. The study aims to investigate the role of stigmasterol in lung cancer and further explore its possible mechanisms. Methods. Cell Counting Kit-8 assay, 5-ethynyl-2- deoxyuridine (EdU), TUNEL and Flow cytometry were conducted to detect the proliferation and apoptosis of lung cancer cell lines. qRT-PCR and western blot were conducted to detect mRNA and protein levels of caspase-3 and caspase-9. In addition, Gene Ontology, STRING, SWISSMODEL, cellular thermal shift assay (CETSA) and Swiss Target Prediction were used to predict the targets of stigmasterol. Results. Behavioral studies showed that stigmasterol inhibited the proliferation and promoted the apoptosis of lung cancer cells. Further research revealed that retinoic acid-related orphan receptor C (RORC) directly targeted stigmasterol in lung cancer. Interestingly, rescue experiments indicated that RORC overexpression reversed the inhibitory effect of stigmasterol on lung cancer. Conclusion. In our study, we confirmed the functional role of the stigmasterol-RORC axis in lung cancer progression, which provides a latent target for lung cancer treatment.
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    Telocytes and lung disease
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Song, Dongli; Cretoiu, Dragos; Cretoiu, Sanda M.; Wang, Xiangdong
    Telocytes (TCs) represent a new distinct type of interstitial cells found in many organs, including lungs. TCs are mainly defined by a small cellular body from which arise very long (hundreds of micrometers) extensions named telopodes. During the last years, TCs were characterized in respect with their microRNA profiles, gene features and proteome signatures. Also, the ultrastructural 3D configuration was further elucidated by the aid of the FIB-SEM technology. TCs are able to communicate by homo- and heterocellular contacts with neighboring cells and are also able to transfer genetic information and signaling molecules to influence other cells by means of extracellular vesicle release. However, the exact function of lung TCs remains unclear. Here, we review the potential significance of TCs in the pathogenesis of pulmonary diseases. We will also discuss some future possibilities for targeting TCs as a potential therapeutic strategy.
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    Tumor necrosis factor receptor-associated protein 1 promotes aerobic glycolysis and cisplatin resistance by regulating the Wnt/β-catenin signaling pathway in lung cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Li, Ruijie; Lv, Mengguo; Liu, Juan; Sun, Qian; Biología Celular e Histología
    In this study, we investigated the effects of tumor necrosis factor receptor-associated protein 1 (TRAP1) on aerobic glycolysis in cisplatin-resistant lung cancer cells and explored the underlying mechanism. TRAP1 expression levels were determined in cisplatin-resistant lung cancer tissues and A549/CDDP cells. Subsequently, TRAP1 expression in A549/CDDP cells was silenced via small interfering RNA transfection. Moreover, changes in lactate content, glucose consumption, expression levels of lactate dehydrogenase A (LDHA), hexokinase 2 (HK2), and pyruvate kinase M2 (PKM2), and sensitivity to cisplatin were analyzed. Specifically, the Wnt/β-catenin signaling pathway was examined using the Wnt/β-catenin activator, BML-284. TRAP1 expression levels were higher in cisplatin-resistant tissues and A549/CDDP cells than in cisplatin-sensitive tissues and A549 cells (p<0.05). Moreover, the lactate content, glucose consumption, LDHA, HK2, PKM2 expression levels, and half-maximal inhibitory concentration of cisplatin were all significantly decreased after TRAP1 silencing (p<0.05). Compared with A549 cells, the Wnt/β-catenin pathway was activated in A549/CDDP cells, which was inhibited via TRAP1 silencing. BML-284 reversed the effects of TRAP1 silencing on the aerobic glycolysis and cisplatin sensitivity of A549/CDDP cells. Our findings suggest that TRAP1 affects the cisplatin resistance of lung cancer, possibly by regulating aerobic glycolysis via the Wnt/β-catenin pathway.
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    Tumors derived from lung cancer cells respond differently to treatment with sodium valproate (a HDAC inhibitor) in a chicken embryo chorioallantoic membrane model
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Diržiuvienė, Raminta; Šlekienė, Lina; Palubinskienė, Jolita; Balnytė, Ingrida; Lasienė, Kristina; Stakišaitis, Donatas; Valančiūtė, Angelija
    Lung cancer is the most frequent cause of cancer death. Some human lung malignant tumors have a combined small-cell lung cancer (SCLC) and nonsmall-cell lung cancer (NSCLC) histology, with tumor cell phenotype changing during tumor progression. Valproic acid is used as an anti-seizure medication to treat migraine, and bipolar mood disorders. Recently, its efficacy as an adjuvant therapy was shown in cancer due to its histone deacetylase (HDAC) inhibitory property. HDACs are upregulated in lung tumors, and HDAC inhibitors, including valproic acid, inhibit endothelial cell proliferation in vitro and in vivo and have antiproliferative and antimigratory properties. We tested valproic acid for possible antiangiogenic and antimigratory effects on experimental lung tumors grafted onto the chicken embryo chorioallantoic membrane (CAM). Tumors were formed from two NSCLC cell lines and a single SCLC cell line. To investigate tumor and CAM interactions, in vivo biomicroscopy, visualization of blood vessels with injected fluorescent dextran, histological, immunohistochemical and histomorphometric methods were applied. Our results showed that a sodium valproate (NaVP) treatment-induced a dose-dependent decrease of experimental tumor invasion into the CAM mesenchyme and a reduction in angiogenesis. Both the invasion and the angiogenic response were dependent on the type of cell line used: invasion and angiogenesis of tumors derived from A549 and NCI-H146 cell lines responded to increasing doses of NaVP from 4 to 8 mM, whereas Sk_Lu_1 cells response were antimigratory and antiangiogenic when NaVP was used up to 6 mM. When 8mM NaVP was used, stimulated invasion and angiogenesis in tumors from Sk_Lu_1 cells were observed.