Telmisartan induces osteosarcoma cells growth inhibition and apoptosis via suppressing mTOR pathway

Abstract

Osteosarcoma (OS) is a commonly occurring primary malignant bone cancer with serious impact and high mortality, yet effective and safe therapy method not available. The aim of the present study was to elucidate the antitumor effect of telmisartan on human osteosarcoma cells in vitro and its underlying mechanism. The proliferation effect of osteosarcoma cell lines U2OS was examined by Cell Counting Kit-8. The invasive and migratory capabilities were determined by transwell invasion and migration assay. The percentage of apoptotic cells were detected by flow cytometric analysis and proteins related to apoptosis including Bax, Bcl-2 and Cleaved Caspase-3 were examined by western blotting. The expressions of mammalian target of rapamycin (mTOR) signaling relevant molecules were detected by western blot assay. Telmisartan treatment caused dose-dependent and time-dependent inhibition of proliferation and inducing anti-migration, anti-invasiveness and apoptosis of U2OS cells. The induction of apoptosis was confirmed concurring with the altered expression of proteins associated with the apoptosis. Mechanistically, telmisartan suppresses mTOR activation. Telmisartan can impede the growth, invasion, migration and induce the apoptosis of U2OS cell probably through inhibiting the mTOR signaling pathway activation. Thus, telmisartan is a potential drug for the prevention and treatment of human osteosarcomal cancer.

Keywords

• telmisartan
• osteosarcoma
• mtor signaling
• proliferation
• apoptosis