Role of the Akt/mTOR survival pathway in cisplatin resistance in ovarian cancer cells.
Role of the Akt/mTOR survival pathway in cisplatin resistance in ovarian cancer cells.
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DOI：
10.1016/j.bbrc.2010.03.029
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发表时间：
2010-04-09
影响因子：
3.1
通讯作者：
Wu, Gen Sheng
中科院分区：
文献类型：
--
作者：
Peng, Dong-Jun;Wang, Juan;Zhou, Jun-Ying;Wu, Gen Sheng
癌细胞中顺铂耐药的机制尚未完全了解。在这里，我们表明Akt/mTOR生存通路在人卵巢癌细胞顺铂耐药中起着重要作用。具体而言，我们发现顺铂治疗激活Akt/mTOR存活途径，并且通过PI 3 K抑制剂LY 294002或Akt敲低抑制该途径可使卵巢癌细胞对顺铂敏感。此外，我们产生了顺铂耐药细胞，并发现耐药细胞表达更高水平的活化Akt相比，其顺铂敏感的同行。重要的是，Akt或mTOR的抑制使耐药细胞对顺铂诱导的凋亡敏感。总之，我们的数据表明Akt/mTOR通路的激活阻止顺铂诱导的细胞凋亡，导致顺铂耐药。因此，我们的研究表明，顺铂耐药可以通过靶向Akt/mTOR生存途径在人卵巢癌细胞克服。
The mechanism of cisplatin resistance in cancer cells is not fully understood. Here, we show that the Akt/mTOR survival pathway plays an important role in cisplatin resistance in human ovarian cancer cells. Specifically, we found that cisplatin treatment activates the Akt/mTOR survival pathway and that inhibition of this pathway by the PI3 K inhibitor LY294002 or knockdown of Akt sensitizes ovarian cancer cells to cisplatin. Furthermore, we generated cisplatin-resistant cells and found that resistant cells express a higher level of activated Akt as compared to their cisplatin sensitive counterparts. Importantly, inhibition of Akt or mTOR sensitized resistant cells to cisplatin-induced apoptosis. Taken together, our data indicate that activation of the Akt/mTOR pathway prevents cisplatin-induced apoptosis, leading to cisplatin resistance. Therefore, our study suggests that cisplatin resistance can be overcome by targeting the Akt/mTOR survival pathway in human ovarian cancer cells.
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