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

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

  • J Oral Biosci. 2024 Sep 6:S1349-0079(24)00198-1. doi: 10.1016/j.job.2024.09.003.
Luo-Yun Wu 1,  Bor-Chyuan Su 2,  Hsin-Hsien Yu 3,  Chih-Cheng Cheng 4,  Chia-Chi Tsai 5,  Pei-Ling Hsu 6,  Chu-Wan Lee 7
Affiliations

Affiliations

  • 1 School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • 2 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.
  • 3 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.
  • 4 Division of General Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
  • 5 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
  • 6 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.
  • 7 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.
PMID: 39245205 DOI: 10.1016/j.job.2024.09.003
Abstract

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.

Keywords

EGFR; Losartan; cell proliferation; oral cancer.

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