Anti-proliferative effect of metformin on a feline injection site sarcoma cell line independent of Mtor inhibition

• Published in: Research in veterinary science 2017-10, Vol.114, p.74-79
• Main Authors: Pierro, J., Saba, C., McLean, K., Williams, R., Karpuzoglu, E., Prater, R., Hoover, K., Gogal, R.
• Format: Article
• Language: English
• Subjects: AMP; AMP-activated protein kinase; Animals; Antidiabetics; Apoptosis; Apoptosis - drug effects; Breast cancer; Cancer; Cancer therapies; Cat Diseases - drug therapy; Cat Diseases - etiology; Cats; Cell cycle; Cell death; Cell growth; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemotherapy; Cytometry; Cytotoxicity; Diabetes; Dose-Response Relationship, Drug; Fatty acids; Feline; Flow cytometry; Growth factors; Humans; Hypoglycemic Agents - pharmacology; In vitro; Inhibition; Inhibitory Concentration 50; Injection; Injection site sarcoma; Injections - adverse effects; Injections - veterinary; Insulin resistance; Kinases; Medical prognosis; Metformin; Metformin - pharmacology; Mortality; Ovarian cancer; Proteins; Rapamycin; Sarcoma; Sarcoma - pathology; Sarcoma - veterinary; Signal transduction; Studies; Thyroid cancer; TOR protein; TOR Serine-Threonine Kinases - antagonists & inhibitors; Vaccine-associated sarcoma; Veterinary medicine
• ISSN: 0034-5288; 1532-2661
• DOI: 10.1016/j.rvsc.2017.03.003

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. •Metformin decreases feline ISS cell viability in a dose-dependent fashion in the cell line tested.•It is unclear if apoptosis or necrosis is the mechanism of cellular death in feline ISS-treated cells.•Inhibition of mTOR does not appear to play a role in these effects.