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.

查看原文本刊更多论文

Phospho-cofilin通过yes相关蛋白抑制预测法舒地尔治疗口腔鳞状细胞癌的效率。

目的：本研究评估了法舒地尔（一种rho相关的含卷曲卷曲蛋白激酶（ROCK）抑制剂）抑制口腔鳞状细胞癌（OSCC）生长的潜力，并探索了磷酸化-cofilin作为预测法舒地尔在OSCC治疗效果的潜在生物标志物。设计：109例OSCC患者提供组织样本进行磷酸化-cofilin表达分析和生存分析。本研究考察了法舒地尔对OSCC细胞系HSC-3、UM1和CAL33的影响，通过各种体外和体内实验评估肿瘤生长抑制作用。通过RNA测序、q-PCR和免疫荧光技术探索ROCK抑制反应及其下游机制。结果：OSCC组织中高磷酸化-cofilin表达与患者预后差相关，是ROCK活性的可靠生物标志物。法舒地尔抑制OSCC细胞系的生长，特别是那些高磷酸化-cofilin表达的细胞系。ROCK抑制导致yes相关蛋白（YAP）活性下调，导致体外和体内肿瘤增殖受到抑制，细胞凋亡增加。结论：法舒地尔抑制ROCK/phospho-cofilin/YAP可抑制OSCC的增殖，而phospho-cofilin可能是OSCC的潜在生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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