Role of the Akt/mTOR survival pathway in cisplatin resistance in ovarian cancer cells |
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Authors: | Dong-Jun Peng Jun-Ying Zhou |
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Institution: | Program in Molecular Biology and Genetics, Karmanos Cancer Institute, Department of Pathology, Wayne State University School of Medicine, 110 East Warren Ave., Detroit, MI 48201, USA |
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Abstract: | 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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Keywords: | Cisplatin resistance Ovarian cancer cells Akt mTOR Apoptosis |
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