%0 Journal Article
%T Metformin Sensitizes Leukemia Cells to Vincristine via Activation of AMP-activated Protein Kinase
%A Chunyan Zhang
%A Johann Bergholz
%A Juan Ao
%A Linfeng Gao
%A Min Lin
%A Min Wu
%A Xiaodong Wang
%A Yong Yi
%A Yujun Zhang
%A Zhi-Xiong Jim Xiao
%J Journal of Cancer
%D 2017
%I Ivyspring International Publisher
%R 10.7150/jca.19873
%X 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 AMPK¦Į1 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 AMPK¦Į1 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.
%K Leukemia
%K Vincristine
%K Metformin
%K AMP-activated Protein Kinase
%K Apoptosis
%K Combination Therapy
%U http://www.jcancer.org/v08p2636.htm