Blockage of glutaminolysis enhances the sensitivity of ovarian cancer cells to PI3K/mTOR inhibition involvement of STAT3 signaling

• DOI: 10.1007/s13277-016-4984-3
• Publication Date: 2016-02-19T01:12:57Z
• Authors: Lili Guo; Bo Zhou; Zhengqing Liu; Ying Xu; Hao Lu; Meng Xia; Ensong Guo; Wanying Shan; Gang Chen; Changyu Wang
• Keywords: Glutaminolysis; mTORC2; RPTOR

The PI3K/Akt/mTOR axis in ovarian cancer is frequently activated and implicated tumorigenesis. Specific targeting of this pathway therefore an attractive therapeutic approach for cancer. However, cells are resistant to PP242, a dual inhibitor mTORC1 mTORC2. Interestingly, blockage GLS1 with selective inhibitor, CB839, or siRNA dramatically sensitized the PP242-induced cell death, as evident from increased PARP cleavage. anti-cancer activity CB-839 PP242 was abrogated by addition TCA cycle product α-ketoglutarate, indicating critical function survival. Finally, glutaminolysis inhibition apoptosis synergistically priming mTOR PP242. significantly reduced phosphorylated STAT3 expression cells. These findings show that glutamine addiction via offers potential novel strategy overcome resistance inhibition.