Anti-proliferative effect of metformin on a feline injection site sarcoma cell line independent of Mtor inhibition.
Metformin is an oral hypoglycemic drug that has been shown to inhibit cancer cell proliferation via up-regulation of AMPK (AMP-activated protein kinase), and possibly inhibition of mTOR (mammalian target of rapamycin). The purpose of this study was to evaluate the effects of metformin on a feline injection site sarcoma cell line. Cells from a feline injection site sarcoma cell line were treated with metformin at varied concentrations. A dose-dependent decrease in cell viability following metformin treatment was observed, with an IC50 of 8.0mM. Using flow cytometry, the mechanism of cell death was determined to be apoptosis or necrosis. To evaluate the role of mTOR inhibition in metformin-induced cell death, Western blot was performed. No inhibition of mTOR or phosphorylated mTOR was found. Although metformin treatment leads to apoptotic or necrotic cell death in feline injection site sarcoma cells, the mechanism does not appear to be mediated by mTOR inhibition.
University of Georgia, College of Veterinary Medicine, Department of Small Animal Medicine and Surgery, 2200 College Station Road, Athens, GA 30602, United States.
J
J
Pierro
University of Georgia, College of Veterinary Medicine, Department of Small Animal Medicine and Surgery, 2200 College Station Road, Athens, GA 30602, United States. Electronic address: csaba@uga.edu.
C
C
Saba
University of Georgia, College of Veterinary Medicine, Department of Veterinary Biosciences and Diagnostic Imaging, 501 DW Brooks Drive, Athens, GA 30602, United States.
K
K
McLean
University of Georgia, College of Veterinary Medicine, Department of Veterinary Biosciences and Diagnostic Imaging, 501 DW Brooks Drive, Athens, GA 30602, United States.
R
R
Williams
University of Georgia, College of Veterinary Medicine, Department of Veterinary Biosciences and Diagnostic Imaging, 501 DW Brooks Drive, Athens, GA 30602, United States.
E
E
Karpuzoglu
University of Georgia, College of Veterinary Medicine, Department of Small Animal Medicine and Surgery, 2200 College Station Road, Athens, GA 30602, United States.
R
R
Prater
University of Georgia, College of Veterinary Medicine, Department of Small Animal Medicine and Surgery, 2200 College Station Road, Athens, GA 30602, United States.
K
K
Hoover
University of Georgia, College of Veterinary Medicine, Department of Veterinary Biosciences and Diagnostic Imaging, 501 DW Brooks Drive, Athens, GA 30602, United States.
R
R
Gogal
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002371:Cat Diseases / Q000188:drug therapy* / Q000209:etiology; D002415:Cats; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007267:Injections / Q000009:adverse effects / Q000662:veterinary; D008687:Metformin / Q000494:pharmacology*; D012509:Sarcoma / Q000473:pathology / Q000662:veterinary*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
D007004:Hypoglycemic Agents; D008687:Metformin; D058570:TOR Serine-Threonine Kinases
Cancer; Feline; In vitro; Injection site sarcoma; Metformin; Vaccine-associated sarcoma