Xiaoyan Li, B Wang, Guoyan Yu, Xiaochen Qiao, Ziyang Huang, Yuxin Yang, Junjun Li, Jinhua Xu, Liting Bai, Huimin Li, Xinyu Song, Lixia Chen, Lili Zhao, Yongming Yang, Yong Zhang, Jinmiao Tian, Xihua Yang
Background Cordyceps sinensis is a well-known traditional Chinese medicine with antitumor activity. Isaria felina (IF) is a novel fungus isolated from the fruiting bodies of Cordyceps sinensis. IFA was prepared by fermentation and ethanol extraction. This study investigated the antitumor effects of the ethanol extract of IF (IFA) on hepatocellular carcinoma (HCC) using H22 hepatocellular carcinoma cells and a mouse xenograft model. Methods In vitro , CCK-8 assay was used to assess cell viability. Annexin V-PE/7AAD flow cytometry, RT-PCR, and Western blot were performed to detect apoptosis and related pathways. In vivo , H22 tumor-bearing mice were treated with IFA by gavage. TUNEL staining, immunohistochemistry, blood routine, serum biochemistry, and ELISA were applied to evaluate tumor apoptosis, liver function parameters, and immune parameters. Results IFA dose-dependently inhibited H22 cell proliferation. Flow cytometry showed that IFA induced late-stage apoptosis. RT-PCR and Western blot revealed upregulation of P53, Bax, Cyt C, and Caspase-3, and downregulation of Bcl-2, indicating activation of the P53/Bax/Bcl-2/Cyt C/Caspase-3 pathway. In vivo , IFA suppressed tumor growth, increased TUNEL-positive apoptotic cells, and enhanced serum TNF-α while reducing TGF-β, without impairing liver or kidney function. Conclusions IFA inhibits HCC growth by inducing mitochondrial apoptosis via the P53 pathway and by modulating host immunity, highlighting its potential as a natural therapeutic agent for HCC.