Abstract
Esophageal squamous cell carcinoma (ESCC) is the most common primary esophageal malignancy. Telmisartan, an angiotensin II type 1 (AT1) receptor blocker (ARB) and a widely used antihypertensive, has been shown to inhibit proliferation of various cancer types. This study evaluated the effects of telmisartan on human ESCC cell proliferation in vitro and in vivo and sought to identify the microRNAs (miRNAs) involved in these antitumor effects. We examined the effects of telmisartan on three human ESCC cell lines (KYSE150, KYSE180, and KYSE850). Telmisartan inhibited proliferation of these three cell lines by inducing S-phase arrest, which was accompanied by decreased expression of cyclin A2, cyclin-dependent kinase 2, and other cell cycle-related proteins. Additionally, telmisartan reduced levels of phosphorylated ErbB3 and thrombospondin-1 in KYSE180 cells. Furthermore, expression of miRNAs was remarkably altered by telmisartan in vitro. Telmisartan also inhibited tumor growth in vivo in a xenograft mouse model. In conclusion, telmisartan inhibited cell proliferation and tumor growth in ESCC cells by inducing cell-cycle arrest.
Highlights
Esophageal cancer is the seventh most common cancer worldwide; more than half a million new cases were diagnosed in 2018, and its mortality is the sixth highest of all cancers [1]
Esophageal cancer is classified into two major types: Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC)
Many genetic abnormalities are associated with ESCC, as are altered expressions of the cell-cycle regulator cyclin and cyclin-dependent kinases (CDKs)
Summary
Esophageal cancer is the seventh most common cancer worldwide; more than half a million new cases were diagnosed in 2018, and its mortality is the sixth highest of all cancers [1]. Compared with our present study, this discrepancy may reflect differences of differentiation, or cell type in in vitro models This finding suggests that these proteins—major cell-cycle regulators—could facilitate the telmisartan-mediated antitumor effect by inducing S-phase arrest in ESCC cells. Telmisartan did not significantly increase activated caspase-3 in KYSE180 cells These data suggest that telmisartan mainly inhibits ESCC cell proliferation by inducing cell-cycle arrest but not apoptosis. To find out which miRNAs are associated with the antitumor effects of telmisartan, we used miRNA expression assays Their results showed that the expression of miRNA in telmisartan-treated ESCC cells were significantly different from that in control cells (36 upregulated and 23 downregulated). Our results indicate that telmisartan inhibits human ESCC cell proliferation and tumor growth by inducing S-phase cell-cycle arrest via regulation of cell-cycle-related proteins
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