The Angiotensin II Type 1 Receptor Antagonist Telmisartan Inhibits Cell Proliferation and Tumor Growth of Esophageal Adenocarcinoma Via the AMPKα/mTOR Pathway in Vitro and in Vivo

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Jan 5

PMID 28052030

Citations 25

Authors

Shintaro Fujihara

Asahiro Morishita

Kana Ogawa

Tomoko Tadokoro

Taiga Chiyo

Kiyohito Kato

Hideki Kobara

Hirohito Mori

Hisakazu Iwama

Tsutomu Masaki

Affiliations

Soon will be listed here.

Abstract

Telmisartan, a widely used antihypertensive drug, is an angiotensin II type 1 (AT1) receptor blocker (ARB). This drug inhibits cancer cell proliferation, but the underlying mechanisms in various cancers, including esophageal cancer, remain unknown. The aim of the present study was to evaluate the effects of telmisartan on human esophageal cancer cell proliferation in vitro and in vivo. We assessed the effects of telmisartan on human esophageal adenocarcinoma (EAC) cells using the cell lines OE19, OE33, and SKGT-4. Telmisartan inhibited the proliferation of these three cell lines via blockade of the G0 to G1 cell cycle transition. This blockade was accompanied by a strong decrease in cyclin D1, cyclin E, and other cell cycle-related proteins. Notably, the AMP-activated protein kinase (AMPK) pathway, a fuel sensor signaling pathway, was enhanced by telmisartan. Compound C, which inhibits the two catalytic subunits of AMPK, enhanced the expression of cyclin E, leading to G0/G1 arrest in human EAC cells. In addition, telmisartan reduced the phosphorylation of epidermal growth factor receptor (p-EGFR) and ERBB2 in vitro. In our in vivo study, intraperitoneal injection of telmisartan led to a 73.2% reduction in tumor growth in mice bearing xenografts derived from OE19 cells. Furthermore, miRNA expression was significantly altered by telmisartan in vitro and in vivo. In conclusion, telmisartan suppressed human EAC cell proliferation and tumor growth by inducing cell cycle arrest via the AMPK/mTOR pathway.

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