Antihypertensive agent losartan promotes tongue squamous cell carcinoma cell proliferation via EGFR/ERK1/2/cyclin D1 signaling axis.

Autor: Wu LY; School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: b101109062@tmu.edu.tw., Su BC; Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan., Yu HH; Division of General Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Division of General Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan., Cheng CC; Division of General Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan., Tsai CC; School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan., Hsu PL; Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, 80708, Taiwan., Lee CW; Department of Nursing, National Tainan Junior College of Nursing, 78, Section 2, Minzu Road, West Central District, Tainan, 70007, Taiwan. Electronic address: chuwan@ntin.edu.tw.
Jazyk: angličtina
Zdroj: Journal of oral biosciences [J Oral Biosci] 2024 Dec; Vol. 66 (4), pp. 74-80. Date of Electronic Publication: 2024 Sep 07.
DOI: 10.1016/j.job.2024.09.003
Abstrakt: Objective: To study the effects of losartan, an angiotensin II receptor blocker, in the SCC4 and SCC25 human tongue squamous cell carcinoma cell lines.
Methods: Cell proliferation was measured by MTS/PMS activity and trypan blue exclusion assays. The levels of the cell proliferation marker, cyclin D1, were analyzed by western blotting. Apoptosis was assessed by caspase-3 activation and Annexin V-FITC/propidium iodide double staining. Activation of epidermal growth factor receptor (EGFR) and ERK1/2 was validated by western blotting.
Results: Moderate concentrations of losartan enhanced the proliferation of SCC4 and SCC25 cells. However, high losartan concentrations induced apoptosis in SCC4 cells. Losartan activated the EGFR/ERK1/2/cyclin D1 signaling axis, which in turn promoted cell proliferation. Afatinib (EGFR inhibitor) and U0126 (ERK1/2 inhibitor) abolished losartan-induced cell proliferation. In contrast, UC2288 (p21 inhibitor) enhanced it.
Conclusions: Losartan exhibited dual effects on tongue squamous cell carcinoma cells. Moderate losartan concentrations facilitated cell proliferation, whereas high concentrations induced cytotoxicity in tongue carcinoma cells.
Competing Interests: Declaration of competing interest The authors declare that they have no competing interest for this article.
(Copyright © 2024 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: