期刊
CANCER BIOLOGY & THERAPY
卷 16, 期 10, 页码 1548-1556出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15384047.2015.1071738
关键词
artesunate; chemosensitization; homologous recombination repair; ovarian cancer; RAD51
类别
资金
- National Basic Research Program of China (973 Program) [2011CB966200]
- National Natural Science Foundation [81372241, 81171968, 31371369]
- International Science & Technology Cooperation Program of China [2013DFG32700]
- State Program of National Natural Science Foundation of China for Innovative Research Group [81321061]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据