Antidiabetic drug metformin mitigates ovarian cancer SKOV3 cell growth by triggering G2/M cell cycle arrest and inhibition of m-TOR/PI3K/Akt signaling pathway.
Metformin is one of most extensively prescribed oral hypoglycemic drug and has received increased attention in recent times for its antitumorigenic potential. Many possible mechanisms have been proposed for the ability of metformin to overturn cancer growth in vitro and in vivo. The objective of the present study was to evaluate the anticancer activity of metformin against ovarian SKOV3 cancer cells.



Anticancer activity and IC50 value of metformin were determined by MTT assay. Reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and effect on cycle were determined by flow cytometry. Protein expression was estimated by Western blotting.



Results indicated that metformin exhibited an IC50 of 20 mM against ovarian SKOV3 cancer cell line. Metformin also caused DNA damage in SKOV3 cells and also prompted ROS-mediated alterations in mitochondrial membrane potential. Nonetheless, it triggered cell cycle arrest of SKOV3 at G2/M checkpoint. The activation of the PI3K/AKT/mTOR pathway plays a vital role in ovarian cancer tumorigenesis, progression and chemotherapy resistance. The results showed that metformin significantly inhibited the expression levels of key proteins of PI3K/Akt/mTOR signaling pathway.



We propose that metformin exhibits anticancer activity in SKOV3 cells and may prove beneficial in the management of ovarian cancers.
Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. honghe147@hotmail.com.
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D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008687:Metformin / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D007004:Hypoglycemic Agents; D008687:Metformin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt