MicroRNA profiles following telmisartan treatment in pancreatic ductal adenocarcinoma cells
Yoshimi Yamana1, Shintaro Fujihara1, Hideki Kobara1, Kyoko Oura1, Eri Samukawa1, Taiga Chiyo1, Megumi Okamura1, Hiroki Yamana1, Tomoko Tadokoro1, Koji Fujita1, Asahiro Morishita1, Hisakazu Iwama2, Tsutomu Masaki1
1 Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan
2 Life Science Research Center, Faculty of Medicine, Kagawa University, Kagawa, Japan
Department of Gastroenterology and Neurology, Kagawa University Faculty of Medicine/Graduate School of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793
Source of Support: None, Conflict of Interest: None
Background: Pancreatic ductal adenocarcinoma (PDAC) is the most devastating of all cancers with an extremely poor prognosis. It has few effective and reliable therapeutic strategies. Telmisartan, a widely used antihypertensive drug, is an angiotensin II type 1 (AT1) receptor blocker (ARB). Telmisartan inhibits cancer cell proliferation, but the underlying mechanisms in PDAC, remain unknown.
Material and Methods: In the present study, we evaluated the effects of telmisartan on human PDAC cell proliferation in vitro. We assessed the effects of telmisartan on human PDAC cells using the cell lines PK-1 and PANC-1.
Results: Telmisartan inhibited the proliferation of these cells via blockade of the G0 to G1 cell cycle transition. This was accompanied by a strong decrease in cyclin D1. Telmisartan was also shown by receptor tyrosine kinase and angiogenesis arrays to reduce the phosphorylation of epidermal growth factor receptor (EGFR), and miRNA expression was markedly altered by telmisartan in PK-1 cells.
Conclusion: In conclusion, telmisartan inhibits human PDAC cell proliferation by inducing cell cycle arrest. Furthermore, telmisartan significantly altered miRNA expression in vitro. Taken together, our study demonstrated the therapeutic potential of telmisartan and provides molecular mechanistic insights into its anti-tumor effect on PDAC cells.