Inhibition of mTORC1/P70S6K pathway by Metformin synergistically sensitizes Acute Myeloid Leukemia to Ara-C.

AIMS:Chemo-resistance still was the main obstacle for AML patients, more effective and less toxic forms of therapies were desperately needed. Metformin, a classic hypoglycemic drug for diabetes recently delivered us a new identity that it exerted anti-tumor activity through suppressing mTOR in various tumors. But the anti-tumor effect of metformin in AML was not clear. METHODS:In this study, we used CCK8 assay and apoptosis assay to determine the anti-leukemia activity of metformin combined with AraC, and explore the mechanism of the joint role of Ara-C/metformin in AML. We finally used xenograft experiment in mice to determine the anti-leukemia effect of Ara-C/metformin in vivo. KEY FINDINGS:We found that metformin could synergistically sensitize AML cells to Ara-C via inhibiting mTORC1/P70S6K pathway. In vivo experiment also verified metformin in aid of Ara-C caused an obviously synergistic anti-tumor effect. SIGNIFICANCE:We firstly found the synergistic anti-tumor effect of Ara-C/metformin in AML through inhibiting mTORC1/P70S6K pathway.