Metformin Sensitizes Leukemia Cells to Vincristine Via Activation of AMP-activated Protein Kinase

Overview

Journal J Cancer

Specialty Oncology

Date 2017 Sep 14

PMID 28900501

Citations 12

Authors

Yong Yi

Linfeng Gao

Min Wu

Juan Ao

Chunyan Zhang

Xiaodong Wang

Min Lin

Johann Bergholz

Yujun Zhang

Zhi-Xiong Jim Xiao

Affiliations

Soon will be listed here.

Abstract

Vincristine is extensively used chemotherapeutic medicine to treat leukemia. However, it remains a critical clinical problem with regard to its toxicity and drug-resistance. AMP-activated protein kinase (AMPK) is an energy sensor that is pivotal in maintaining cell metabolic homeostasis. It is reported that AMPK is involved in vincristine-induced apoptosis. However, whether AMPK is involved in chemotherapy-resistance is largely unclear. It is well-documented that metformin, a widely used medicine to treat type II diabetes, possesses anti-cancer activities, yet whether metformin affects leukemia cell viability via vincristine is unknown. In this study, we showed that both AMPKα1 mRNA and phosphorylated AMPK protein levels were significantly decreased in clinical leukemia samples. We further demonstrated that metformin sensitized leukemia cells to vincristine-induced apoptosis in an AMPK-dependent manner. In addition, knockdown of AMPKα1 significantly reduced the effects of metformin on vincristine-induced apoptosis. Taken together, these results indicate that AMPK activation is critical in metformin effects on vincristine-induced apoptosis and suggest a putative strategy of a combination therapy using metformin and vincristine in treatment of leukemia.

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