Title |
Blockage of glutaminolysis enhances the sensitivity of ovarian cancer cells to PI3K/mTOR inhibition involvement of STAT3 signaling
|
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Published in |
Tumor Biology, February 2016
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DOI | 10.1007/s13277-016-4984-3 |
Pubmed ID | |
Authors |
Lili Guo, Bo Zhou, Zhengqing Liu, Ying Xu, Hao Lu, Meng Xia, Ensong Guo, Wanying Shan, Gang Chen, Changyu Wang |
Abstract |
The PI3K/Akt/mTOR axis in ovarian cancer is frequently activated and implicated in tumorigenesis. Specific targeting of this pathway is therefore an attractive therapeutic approach for ovarian cancer. However, ovarian cancer cells are resistant to PP242, a dual inhibitor of mTORC1 and mTORC2. Interestingly, blockage of GLS1 with a selective inhibitor, CB839, or siRNA dramatically sensitized the PP242-induced cell death, as evident from increased PARP cleavage. The anti-cancer activity of CB-839 and PP242 was abrogated by the addition of the TCA cycle product α-ketoglutarate, indicating the critical function of GLS1 in ovarian cancer cell survival. Finally, glutaminolysis inhibition activated apoptosis and synergistically sensitized ovarian cancer cells to priming with the mTOR inhibitor PP242. GLS1 inhibition significantly reduced phosphorylated STAT3 expression in ovarian cancer cells. These findings show that targeting glutamine addiction via GLS1 inhibition offers a potential novel therapeutic strategy to overcome resistance to PI3K/Akt/mTOR inhibition. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 32 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 8 | 25% |
Researcher | 6 | 19% |
Student > Bachelor | 4 | 13% |
Other | 3 | 9% |
Student > Master | 3 | 9% |
Other | 3 | 9% |
Unknown | 5 | 16% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 12 | 38% |
Agricultural and Biological Sciences | 5 | 16% |
Medicine and Dentistry | 3 | 9% |
Immunology and Microbiology | 2 | 6% |
Neuroscience | 2 | 6% |
Other | 2 | 6% |
Unknown | 6 | 19% |