Huang Chen, Zhang Chenliang, Li Jiajin, Duan Yichun, Tang Qiulin, Bi Feng
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.
Division of Abdominal Tumor Multimodality Treatment, West China Hospital, Sichuan University, Cancer Center, 610041, Chengdu, Sichuan Province, China.
Cell Biol Toxicol. 2025 Jan 28;41(1):35. doi: 10.1007/s10565-024-09979-x.
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.
索拉非尼（Sora）是晚期肝细胞癌（HCC）患者的一线治疗药物。它能显著提高晚期HCC患者的生存率，但治疗过程中易产生耐药性，因此治疗效果极为有限。在此，我们证明肝细胞癌细胞中蛋白激酶p38γ的表达升高会降低肿瘤细胞对Sora的敏感性。吡非尼酮（PFD）可通过特异性靶向p38γ增强Sora对肝细胞癌的抑制作用。我们的研究进一步发现，吡非尼酮可通过抑制p38γ增强的自噬，协同增强Sora对肝细胞癌的抗癌作用。综上所述，我们的研究结果表明，吡非尼酮可与Sora协同作用，增强其对肝细胞癌的抗肿瘤作用，从而为Sora介导的肿瘤治疗提供一种新的治疗方法。
