Phospho-cofilin predicts efficiency of Fasudil for oral squamous cell carcinoma treatment through Yes-associated protein inhibition

IF 2.2 4区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE

Archives of oral biology Pub Date : 2025-01-29 DOI:10.1016/j.archoralbio.2025.106185

Ying Wu , Yuchen Jiang , Lanxin Jiang , Yang Peng , Tong Zhou , Xiaoqiang Xia , Feifei Hou , Qiuyun Yuan , Lu Ye , Weideng Wei , Jiuge Zhang , Qianming Chen , Xiaodong Feng

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引用次数: 0

Abstract

Objectives

This study evaluates Fasudil, a Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor, for its potential to inhibit oral squamous cell carcinoma (OSCC) growth and explores phospho-cofilin as a potential biomarker for prediction treatment efficiency of Fasudil in OSCC.

Design

A cohort of 109 OSCC patients provided tissue samples for phospho-cofilin expression analysis and survival analysis. The study examined the effect of Fasudil on OSCC cell lines HSC-3, UM1, and CAL33, assessing tumor growth inhibition through various in vitro and in vivo experiments. ROCK inhibition response and downstream mechanisms were explored by RNA sequencing, q-PCR, and immunofluorescence.

Results

High phospho-cofilin expression in OSCC tissues correlated with poor patient outcomes and was a reliable biomarker for ROCK activity. Fasudil inhibited growth in OSCC cell lines, particularly those with high phospho-cofilin expression. ROCK inhibition led to downregulation of Yes-associated protein (YAP) activity, resulting in suppressed tumor proliferation and increased apoptosis both in vitro and in vivo.

Conclusions

Inhibition of ROCK/phospho-cofilin/YAP by Fasudil could suppress OSCC proliferation, while phospho-cofilin served as a potential biomarker of OSCC.

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来源期刊

Archives of oral biology 医学-牙科与口腔外科

CiteScore

5.10

自引率

3.30%

发文量

177

审稿时长

26 days

期刊介绍： Archives of Oral Biology is an international journal which aims to publish papers of the highest scientific quality in the oral and craniofacial sciences. The journal is particularly interested in research which advances knowledge in the mechanisms of craniofacial development and disease, including: Cell and molecular biology Molecular genetics Immunology Pathogenesis Cellular microbiology Embryology Syndromology Forensic dentistry