Metformin Sensitizes Leukemia Cells to Vincristine via Activation of AMP-activated Protein Kinase
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Yi, Yong
Gao, Linfeng
Wu, Min
Ao, Juan
Zhang, Chunyan
Wang, Xiaodong
Lin, Min
Zhang, Yujun
Xiao, Zhi-Xiong Jim
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https://doi.org/10.7150/jca.19873Metadata
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Yi, Yong, Linfeng Gao, Min Wu, Juan Ao, Chunyan Zhang, Xiaodong Wang, Min Lin, Johann Bergholz, Yujun Zhang, and Zhi-Xiong Jim Xiao. 2017. “Metformin Sensitizes Leukemia Cells to Vincristine via Activation of AMP-activated Protein Kinase.” Journal of Cancer 8 (13): 2636-2642. doi:10.7150/jca.19873. http://dx.doi.org/10.7150/jca.19873.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595093/pdf/Terms of Use
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