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 (C) 2010 Elsevier Inc All rights reserved