机构:[1]Center of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610064. China[2]Hematology Department, Outpatient Department, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, 610072, China四川省人民医院[3]Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China[4]Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
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 alpha 1 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 alpha 1 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.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81330054, 81520108020]; Science and Technology Department of Sichuan Province [2014SZ20116]
第一作者机构:[1]Center of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610064. China
共同第一作者:
通讯作者:
通讯机构:[1]Center of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610064. China[*1]College of Life Sciences, Sichuan University, Chengdu, 610064, China
推荐引用方式(GB/T 7714):
Yi Yong,Gao Linfeng,Wu Min,et al.Metformin Sensitizes Leukemia Cells to Vincristine via Activation of AMP-activated Protein Kinase[J].JOURNAL OF CANCER.2017,8(13):2636-2642.doi:10.7150/jca.19873.
APA:
Yi, Yong,Gao, Linfeng,Wu, Min,Ao, Juan,Zhang, Chunyan...&Xiao, Zhi-Xiong Jim.(2017).Metformin Sensitizes Leukemia Cells to Vincristine via Activation of AMP-activated Protein Kinase.JOURNAL OF CANCER,8,(13)
MLA:
Yi, Yong,et al."Metformin Sensitizes Leukemia Cells to Vincristine via Activation of AMP-activated Protein Kinase".JOURNAL OF CANCER 8..13(2017):2636-2642