title: AMP-activated protein kinase is required for cell survival and growth in HeLa-S3 cells in vivo.
abstract: Activation of the AMP-dependent protein kinase (AMPK) is linked to cancer cell survival in a variety of cancer cell lines, particularly under conditions of stress. As a potent activator of AMPK, metformin has become a hot topic of discussion for its effect on cancer cell. Here, we report that AMPK activated by metformin promotes HeLa-S3 cell survival and growth in vivo. Our results show that metformin inhibited cell proliferation in MCF-7 cells, but not in LKB1-deficient HeLa-S3 cells. Re-expression of LKB-1 in HeLa-S3 cells restored the growth inhibitory effect of metformin, indicating a requirement for LKB-1 in metformin-induced growth inhibition. Moreover, AMPK activation exerted a protective effect in HeLa-S3 cells by relieving ER stress, modulating ER Ca(2+) storage, and finally contributing to cellular adaptation and resistance to apoptosis. Our findings identify a link between AMPK activation and cell survival in HeLa-S3 cells, which demonstrates a beneficial effect of AMPK activated by metformin in cancer cell, and suggests a discrete re-evaluation on the role of metformin/AMPK activation on tumor cell growth, proliferation, and on clinical application in cancer therapy.
authors.affiliation: Section of Cell Biology and Genetics, Shantou University Medical College, Guangdong, China; The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Guangdong, China.
authors.forename: Xuhong
authors.initials: X
authors.lastname: Song
authors.forename: Dongyang
authors.initials: D
authors.lastname: Huang
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaokang
authors.initials: X
authors.lastname: Pan
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Liang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects*; D006367:HeLa Cells / Q000201:enzymology* / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D008687:Metformin / Q000494:pharmacology*
chemical_list: D008687:Metformin; D055372:AMP-Activated Protein Kinases; D002118:Calcium
keywords: AMP-activated kinase; cancer; metformin; proliferation; survival