Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Honokiol inhibits gallbladder cancer proliferation and epithelial mesenchymal transformation by suppressing TMPRSS4-induced PI3K/AKT activation

Conglin Lin, Congren Wang , Mingzhu Li, Zhibing Cai

Department of Hepatobiliary Surgery, First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, Fujian 362000, China;

For correspondence:- Congren Wang Email: Wangcongren_666@163.com Tel:+8659528121291

Accepted: 6 January 2024 Published: 29 January 2024

Citation: Lin C, Wang C, Li M, Cai Z. Honokiol inhibits gallbladder cancer proliferation and epithelial mesenchymal transformation by suppressing TMPRSS4-induced PI3K/AKT activation. Trop J Pharm Res 2024; 23(1):15-25 doi: 10.4314/tjpr.v23i1.3

© 2024 The authors.
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Abstract

Purpose: To determine the role of TMPRSS4 in gallbladder cancer (GBC).

Methods: Quantitative reverse-transcription-polymerase chain reaction (qRT-PCR) and western blotting were used to evaluate the expression of genes, while CCK-8 kit and foci formation assay were used to assess cell growth in GBC-SD and non-obliterative zone (NOZ) cell lines. Cell apoptosis was evaluated by flow cytometry, while cell migration and cell invasion were determined by Transwell assay in GBC-SD and NOZ cell lines.

Results: TMPRSS4 was highly expressed in GBC cells, compared to normal cell, HIBEC. Overexpression of TMPRSS4 enhanced cell viability and 2D foci formation in GBC-SD (stratified) and NOZ; however, knockdown of TMPRSS4 reduced cell proliferation and colony formation in the cell lines (p < 0.05). TMPRSS4 deficiency increased cell apoptosis but its reinforced expression decreased cell apoptosis in GBC cell lines (p < 0.05). Moreover, TMPRSS4 positively regulated cell invasion and migration in GBC cells by upregulating TWIST1, vimentin and N-cadherin. TMPRSS4 also regulated the activation of PI3K/AKT signal pathway. Furthermore, honokiol inhibited gallbladder cancer proliferation and migration, and induced cell apoptosis by suppressing TMPRSS4-induced PI3K/AKT activation (p < 0.05).

Conclusion: TMPRSS4 plays an important role in regulating cell growth, apoptosis and metastasis of gallbladder cancer cells (GBC). Thus, TMPRSS4 might be a new biomarker in gallbladder cancer.

Keywords: Transmembrane Protease Serine 4, Gallbladder cancer, PI3K/AKT, Cell proliferation, Honokiol, Epithelial-mesenchymal transition