Artesunate sensitizes ovarian cancer cells to cisplatin by downregulating RAD51.
Artesunate sensitizes ovarian cancer cells to cisplatin by downregulating RAD51.
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青蒿琥酯通过下调 RAD51 使卵巢癌细胞对顺铂敏感
DOI：
10.1080/15384047.2015.1071738
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发表时间：
2015
影响因子：
3.6
通讯作者：
Shao C
中科院分区：
文献类型：
--
作者：
Wang B;Hou D;Liu Q;Wu T;Guo H;Zhang X;Zou Y;Liu Z;Liu J;Wei J;Gong Y;Shao C
青蒿琥酯是最初用于治疗疟疾的青蒿素的半合成衍生物，最近已被证明具有抗肿瘤特性。青蒿琥酯对癌细胞的细胞毒性作用之一是通过诱导氧化应激和DNA双链断裂（DSBs）介导的。我们在这里报道，除了诱导氧化应激和DSB外，青蒿琥酯还可以下调RAD51并损害卵巢癌细胞中DSB的修复。我们观察到，在青蒿琥酯处理的细胞中，RAD51病灶的形成和同源重组修复（HRR）显著减少。因此，青蒿琥酯和顺铂协同诱导dsb并抑制卵巢癌细胞的克隆形成。RAD51的异位表达能够挽救由青蒿琥酯引起的增加的化学敏感性，证实青蒿琥酯的化学增敏作用至少部分是由RAD51的下调介导的。我们的研究结果表明，青蒿琥酯可以破坏卵巢癌细胞中dsb的修复，因此可以作为化疗中的增敏剂。
Artesunate, a semi-synthetic derivative of arteminisin originally developed for the treatment of malaria, has recently been shown to possess antitumor properties. One of the cytotoxic effects of artesunate on cancer cells is mediated by induction of oxidative stress and DNA double-strand breaks (DSBs). We report here that in addition to inducing oxidative stress and DSBs, artesunate can also downregulate RAD51 and impair DSB repair in ovarian cancer cells. We observed that the formation of RAD51 foci and homologous recombination repair (HRR) were significantly reduced in artesunate-treated cells. As a consequence, artesunate and cisplatin synergistically induced DSBs and inhibited the clonogenic formation of ovarian cancer cells. Ectopic expression of RAD51 was able to rescue the increased chemosensitivity conferred by artesunate, confirming that the chemosensitizing effect of artesuante is at least partially mediated by the downregulation of RAD51. Our results indicated that artesunatecan compromise the repair of DSBs in ovarian cancer cells, and thus could be employed as a sensitizing agent in chemotherapy.