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Cisplatin induced apoptosis of ovarian cancer A2780s cells by activation of ERK/p53/PUMA signals

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dc.contributor.authorSong, Hao
dc.contributor.authorWei, Mei
dc.contributor.authorLiu, Wenfen
dc.contributor.authorShen, Shulin
dc.contributor.authorLi, Jiaqun
dc.contributor.authorWang, Liming
dc.date.accessioned2022-03-24T09:17:10Z
dc.date.available2022-03-24T09:17:10Z
dc.date.issued2018
dc.description.abstractCisplatin (CDDP) is one of the most effective anticancer agents widely used in the treatment of solid tumors, including ovarian cancer. It is generally considered as a cytotoxic drug which kills cancer cells by causing DNA damage, and subsequently inducing apoptosis in cancer cells. However, the underlying mechanisms leading to cell apoptosis remain obscure. In this study, the signaling pathways involved in CDDPinduced apoptosis were examined using CDDP-sensitive ovarian cancer A2780s cells. A2780s cells were treated with CDDP (1.5-3 μg/ml) for 6h, 12h and 24h. Using siRNA targeting P53 and PUMA, and a selective MEK inhibitor, PD98059 to examine the relation between ERK1/2 activation, p53 and PUMA expression after exposure to CDDP, and the effect on CDDP-induced apoptosis. The results shown that treatment of A2780s cells with CDDP (3 μg/ml) for 6-24h induced apoptosis, resulting in the activation of extracellular signalregulated kinase 1/2 (ERK1/2) and accumulation of p53 and PUMA (p53 upregulated modulator of apoptosis) protein. Knockdown of P53 or PUMA by siRNA transfection blocked CDDP-induced apoptosis. Inhibition of ERK1/2 using PD98059, a selective MEK inhibitor, blocked the apoptotic cell death but prevented CDDP-induced accumulation of p53 and PUMA. Knockdown of P53 by siRNA transfection also blocked CDDP-induced accumulation of PUMA. We therefore concluded that CDDP activated ERK1/2 and inducedp53-dependent PUMA upregulation, resulting in triggering apoptosis in A2780s cells. Our study clearly demonstrates that the ERK1/2/p53/PUMA axis is related to CDDP-induced cell death in A2780s cells.es
dc.formatapplication/pdfes
dc.format.extent7es
dc.identifier.doiDOI: 10.14670/HH-11-889
dc.identifier.eisbnHistology and Histopathology, Vol.33, nº1, (2018)es
dc.identifier.issn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/118304
dc.languageenges
dc.publisherUniversidad de Murcia. Departamento de Biología Celular e Histologíaes
dc.relationSin financiación externa a la Universidades
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectOvarian canceres
dc.subjectCisplatines
dc.subjectApoptosises
dc.subjectERK1/2es
dc.subjectP53es
dc.subjectp53 upregulated modulator of apoptosises
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncologíaes
dc.titleCisplatin induced apoptosis of ovarian cancer A2780s cells by activation of ERK/p53/PUMA signalses
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.33, nº1 (2018)