Publication: Cisplatin induced apoptosis of ovarian cancer A2780s cells by activation of ERK/p53/PUMA signals
Authors
Song, Hao ; Wei, Mei ; Liu, Wenfen ; Shen, Shulin ; Li, Jiaqun ; Wang, Liming
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Publisher
Universidad de Murcia. Departamento de Biología Celular e Histología
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DOI
DOI: 10.14670/HH-11-889
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info:eu-repo/semantics/article
Description
Abstract
Cisplatin (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.
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