2. Academic Validation
  3. Targeting p38γ synergistically enhances sorafenib-induced cytotoxicity in hepatocellular carcinoma

Targeting p38γ synergistically enhances sorafenib-induced cytotoxicity in hepatocellular carcinoma

  • Cell Biol Toxicol. 2025 Jan 28;41(1):35. doi: 10.1007/s10565-024-09979-x.
Chen Huang 1 2,  Chenliang Zhang 1 2,  Jiajin Li 3,  Yichun Duan 2,  Qiulin Tang 1,  Feng Bi 4 5
Affiliations

Affiliations

  • 1 Division of Abdominal Tumor Multimodality Treatment, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan Province, China.
  • 2 Division of Abdominal Tumor Multimodality Treatment, West China Hospital, Sichuan University, Cancer Center, 610041, Chengdu, Sichuan Province, China.
  • 3 Sichuan University, West China Hospital of Sichuan University, Chengdu, China.
  • 4 Division of Abdominal Tumor Multimodality Treatment, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan Province, China. bifeng@scu.edu.cn.
  • 5 Division of Abdominal Tumor Multimodality Treatment, West China Hospital, Sichuan University, Cancer Center, 610041, Chengdu, Sichuan Province, China. bifeng@scu.edu.cn.
PMID: 39871031 DOI: 10.1007/s10565-024-09979-x
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.

Keywords

Autophagy; Cell drug resistance; Hepatocellular carcinoma; P38γ; Sorafenib.

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