Bcl2 inhibitor ABT737 reverses the Warburg effect via the Sirt3-HIF1α axis to promote oxidative stress-induced apoptosis in ovarian cancer cells
Compared to normal cells, tumor cells maintain higher concentrations of reactive oxygen species (ROS) to support proliferation, invasion, and metastasis. Chemotherapeutic drugs often induce tumor cell apoptosis by increasing intracellular ROS concentrations to highly toxic levels. ABT737, which inhibits the apoptosis regulator B cell lymphoma 2 (Bcl2), increases the sensitivity of ovarian cancer cells to chemotherapeutic drugs by regulating the glucose metabolism, but the underlying mechanisms remain unclear. Therefore, we aimed to determine whether ABT737 promoted H SKOV3 ovarian cancer cells were treated with H ABT737 downregulated proteins associated with glucose uptake (GLUT1) and glycolysis (LHDA, PKM2 and HK2) via the Sirt3-HIF1α axis, reducing glucose uptake and lactate secretion in SKOV3 cells. This reversed glycolysis in the tumor cells, and promoted H The Bcl2 inhibitor ABT737 enhanced the anti-tumor effect of oxidative stress by reversing the Warburg effect in ovarian cancer cells, providing powerful theoretical support for further clinical applications of Bcl2 inhibitors.
Journal
Life SciencesAuthors
Funding
National Natural Science Foundation of China Grant 81772794National Natural Science Foundation of China Grant 81672948National Natural Science Foundation of China Grant 81472419Jilin Province Industrial Innovation Project Grant 2018C052-7Jilin Provincial Research Foundation for the Development of Science and Technology Projects Grant 20180101102TCJilin Provincial Research Foundation for the Development of Science and Technology Projects Grant 20191004004TCFundamental Research Funds for the Central Universities Funding