{"title":"Targeting p38γ synergistically enhances sorafenib-induced cytotoxicity in hepatocellular carcinoma.","authors":"Chen Huang, Chenliang Zhang, Jiajin Li, Yichun Duan, Qiulin Tang, Feng Bi","doi":"10.1007/s10565-024-09979-x","DOIUrl":null,"url":null,"abstract":"<p><p>Sorafenib (Sora) is a first-line treatment for patients with advanced hepatocellular carcinoma (HCC). It can significantly improve the survival rate of patients with advanced HCC, but it is prone to drug resistance during treatment, so the therapeutic effect is extremely limited. Here, we demonstrate that an elevated expression of protein kinase p38γ in hepatocellular carcinoma cells diminishes the tumor cells' sensitivity to Sora. Pirfenidone (PFD) can augment Sora's inhibitory effect on hepatocellular carcinoma by specifically targeting p38γ. Our study further uncovers that pirfenidone can synergistically boost the anti-hepatocellular carcinoma impact of Sora by impeding the autophagy heightened by p38γ. Taken together, our findings suggest that pirfenidone can work in concert with Sora to intensify its anti-tumor effect on hepatocellular carcinoma, thereby offering a novel therapeutic approach for Sora-mediated tumor treatment.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"35"},"PeriodicalIF":5.3000,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772449/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Biology and Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10565-024-09979-x","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Sorafenib (Sora) is a first-line treatment for patients with advanced hepatocellular carcinoma (HCC). It can significantly improve the survival rate of patients with advanced HCC, but it is prone to drug resistance during treatment, so the therapeutic effect is extremely limited. Here, we demonstrate that an elevated expression of protein kinase p38γ in hepatocellular carcinoma cells diminishes the tumor cells' sensitivity to Sora. Pirfenidone (PFD) can augment Sora's inhibitory effect on hepatocellular carcinoma by specifically targeting p38γ. Our study further uncovers that pirfenidone can synergistically boost the anti-hepatocellular carcinoma impact of Sora by impeding the autophagy heightened by p38γ. Taken together, our findings suggest that pirfenidone can work in concert with Sora to intensify its anti-tumor effect on hepatocellular carcinoma, thereby offering a novel therapeutic approach for Sora-mediated tumor treatment.
期刊介绍：
Cell Biology and Toxicology (CBT) is an international journal focused on clinical and translational research with an emphasis on molecular and cell biology, genetic and epigenetic heterogeneity, drug discovery and development, and molecular pharmacology and toxicology. CBT has a disease-specific scope prioritizing publications on gene and protein-based regulation, intracellular signaling pathway dysfunction, cell type-specific function, and systems in biomedicine in drug discovery and development. CBT publishes original articles with outstanding, innovative and significant findings, important reviews on recent research advances and issues of high current interest, opinion articles of leading edge science, and rapid communication or reports, on molecular mechanisms and therapies in diseases.
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