The Combination of MK-2206 and WZB117 Exerts a Synergistic Cytotoxic Effect Against Breast Cancer Cells

The Combination of MK-2206 and WZB117 Exerts a Synergistic Cytotoxic Effect Against Breast Cancer Cells

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Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in women.Hormone receptor-positive breast cancer is Fresh Fruit usually subjected to hormone therapy, while triple-negative breast cancer is more formidable and poses a therapeutic challenge.Glucose transporters are potential targets for the development of anticancer drugs.In search of anticancer agents whose effect could be enhanced by a GLUT1 inhibitor WZB117, we found that MK-2206, a potent allosteric Akt inhibitor, when combined with WZB117, showed a synergistic effect on growth inhibition and apoptosis induction in breast cancer cells, including ER(+) MCF-7 cells and triple-negative MDA-MB-231 cells.The combination index values at 50% growth inhibition were 0.

45 and 0.21, respectively.Mechanism studies revealed that MK-2206 and WZB117 exert a synergistic cytotoxic effect in both MCF-7 and MDA-MB-231 breast cancer cells by inhibiting Akt phosphorylation and inducing DNA damage.The combination may also compromise DNA damage repair and ultimately lead to Vitamin A apoptosis.Our findings suggest that the combination of Akt inhibitors and GLUT1 inhibitors could be a novel strategy to combat breast cancer.