In vitro metformin anti-neoplastic activity in epithelial ovarian cancer.
OBJECTIVE
Metformin, a commonly used drug in the treatment of type II diabetes, may reduce cancer risk and improve cancer prognosis. We evaluated its effect on epithelial ovarian cancer cell lines.


METHODS
The OVCAR-3 and OVCAR-4 cell lines were exposed to metformin with and without cisplatin. Cytotoxicity assays were performed in triplicates using the Alamar colorimetric assay. Levels of total and phosphorylated AMPK, p70S6K and S6K were evaluated by Western blotting following exposure to metformin.


RESULTS
Metformin induces dose- and time-dependent growth inhibition of OVCAR-3 and OVCAR-4 cell lines. Metformin potentiated the effect of cisplatin in vitro. Metformin growth inhibition was partly abolished by the AMPK inhibitor, compound C. Western blotting demonstrated that metformin at cytotoxic concentrations, induced AMPK phosphorylation and decreased p70S6K and S6K phosphorylation, suggesting the mechanism for its anti-proliferative action.


CONCLUSIONS
Metformin significantly inhibits the growth of ovarian cancer cell lines and potentiates cisplatin. Further pre-clinical studies are being conducted to determine the applicability of metformin in the treatment of ovarian cancer.
Gotlieb
Walter H
WH
Division of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada. walter.gotlieb@mcgill.ca
Saumet
Julio
J
Beauchamp
Marie-Claude
MC
Gu
Jing
J
Lau
Susie
S
Pollak
Michael N
MN
Bruchim
Ilan
I
D000263:Adenylate Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D015153:Blotting, Western; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008687:Metformin / Q000008:administration & dosage / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism
D011720:Pyrazoles; D011743:Pyrimidines; C516138:dorsomorphin; D008687:Metformin; D019893:Ribosomal Protein S6 Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D000263:Adenylate Kinase; D002945:Cisplatin