RNA interference-mediated FANCF silencing sensitizes OVCAR3 ovarian cancer cells to adriamycin through increased adriamycin-induced apoptosis dependent on JNK activation.
RNA interference-mediated FANCF silencing sensitizes OVCAR3 ovarian cancer cells to adriamycin through increased adriamycin-induced apoptosis dependent on JNK activation.
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RNA干扰介导的FANCF沉默通过增加依赖于JNK激活的阿霉素诱导的细胞凋亡使OVCAR3卵巢癌细胞对阿霉素敏感
DOI：
10.3892/or.2013.2295
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发表时间：
2013-05
期刊：
影响因子：
4.2
通讯作者：
Wei MJ
中科院分区：
文献类型：
--
作者：
He M;Sun HG;Hao JY;Li YL;Yu JK;Yan YY;Zhao L;Li N;Wang Y;Bai XF;Yu ZJ;Zheng ZH;Mi XY;Wang EH;Wei MJ
在本研究中，我们通过小干扰RNA(SiRNA)下调卵巢癌细胞中FANCF的表达，以探讨FANCF表达降低对Fanconi贫血(FA)/乳腺癌易感基因(BRCA)通路功能的影响。此外，我们还研究了该方法是否增加卵巢癌细胞对阿霉素的敏感性及其可能的机制(S)。我们发现，沉默FANCF通过减少FANCD2的单素化和病灶形成而使FA/BRCA通路失活，降低FA/BRCA通路的功能，从而抑制OVCAR3细胞的增殖，增加细胞凋亡和DNA损伤。此外，我们还观察到，沉默FANCF增强了ADM在OVCAR3细胞中的抗增殖作用，并增加了ADM在细胞内的积聚，从而使OVCAR3细胞对ADM增敏。此外，沉默FANCF增加了OVCAR3细胞的凋亡，这是由于ADM处理后线粒体膜电位(MMP)引起的DNA损伤降低、JNK激活、细胞色素c释放增加、裂解的caspase-3和依赖JNK激活的多聚(ADP-核糖)聚合酶(PARP)增加所致。总之，我们证实沉默FANCF使OVCAR3卵巢癌细胞对ADM增敏，提示FANCF可能成为卵巢癌治疗策略的潜在靶点。
In the present study, we downregulated FANCF expression by small interfering RNA (siRNA) in OVCAR ovarian cancer cells to address the effects of decreased FANCF expression on the function of the Fanconi anemia (FA)/breast cancer susceptibility gene (BRCA) pathway. Furthermore, we investigated whether this method increases the sensitivity of OVCAR3 cells to adriamycin (ADM) and the possible mechanism(s). We found that silencing of FANCF inactivated the FA/BRCA pathway by decreasing the monoubiquitination and focus formation of FANCD2 and reduced the function of the FA/BRCA pathway, resulting in the inhibition of cell proliferation, increased cell apoptosis and DNA damage in OVCAR3 cells. Moreover, we observed that silencing of FANCF enhanced the antiproliferative effect of ADM in OVCAR3 cells and increased ADM intracellular accumulation consequently sensitizing OVCAR3 cells to ADM. Furthermore, silencing of FANCF increased cell apoptosis of OVCAR3 cells which was caused by decreased mitochondrial membrane potential (MMP)-induced DNA damage, activated Jun N-terminal kinase (JNK), increased release of cytochrome c, increased expression of cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP) dependent on JNK activation following treatment of ADM. Collectively, we confirm that silencing of FANCF sensitizes OVCAR3 ovarian cancer cells to ADM, suggesting that FANCF may serve as a potential target for therapeutic strategies in the treatment of ovarian cancer.
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影响因子：
4.3
作者：
D'Andrea, Alan D.
通讯作者：
D'Andrea, Alan D.
影响因子：
20.3
作者：
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3.3
作者：
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通讯作者：
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