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Telmisartan Induces Osteosarcoma Cells Growth Inhibition and Apoptosis Via Suppressing mTOR Pathway
1The Third Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China.
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.
Insights
Telmisartan effectively inhibits osteosarcoma (OS) cell growth, migration, and invasion while promoting apoptosis. This anticancer effect is linked to the suppression of the mammalian target of rapamycin (mTOR) signaling pathway.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Osteosarcoma (OS) is a primary bone cancer with high mortality and limited effective therapies.
- There is a critical need for novel therapeutic strategies against osteosarcoma.
Purpose of the Study:
- To investigate the antitumor effects of telmisartan on human osteosarcoma cells in vitro.
- To elucidate the underlying molecular mechanisms of telmisartan's action in osteosarcoma.
Main Methods:
- Cell Counting Kit-8 assay for proliferation.
- Transwell assays for invasion and migration.
- Flow cytometry for apoptosis analysis.
- Western blotting for apoptosis-related proteins (Bax, Bcl-2, Cleaved Caspase-3) and mTOR signaling pathway molecules.
Main Results:
- Telmisartan demonstrated dose- and time-dependent inhibition of U2OS osteosarcoma cell proliferation.
- Telmisartan significantly reduced migration and invasion capabilities of U2OS cells.
- Telmisartan induced apoptosis in U2OS cells, evidenced by altered expression of apoptosis-related proteins.
- Telmisartan suppressed the activation of the mammalian target of rapamycin (mTOR) signaling pathway.
Conclusions:
- Telmisartan exhibits significant antitumor activity against osteosarcoma cells in vitro.
- The anticancer effects of telmisartan are mediated through the inhibition of the mTOR signaling pathway.
- Telmisartan represents a potential therapeutic agent for osteosarcoma prevention and treatment.
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