Integrated analyses for identification of a three‐gene signature associated with Chaihu Shugan San formula for hepatocellular carcinoma treatment
Xing J, Tan R, Huang F, Tian N · Journal of Cellular and Molecular Medicine · 2024 April
DOI 10.1111/jcmm.18211
Objective
To investigate the key targets and mechanisms of Chaihu Shugan San against hepatocellular carcinoma and develop a prognostic model for predicting survival in patients with hepatocellular carcinoma.
Conclusions
Chaihu Shugan San may regulate immune-related factors in the tumour microenvironment, reverse immune escape, enhance immune responses through AKT1, MAPK3, and CASP3, and synergistically inhibit hepatocellular carcinoma when combined with sorafenib.
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Insights
Chaihu Shugan San (CSS), a traditional herbal formula, can potentially manage hepatocellular carcinoma (HCC) by regulating immune-related factors in the tumor environment and synergizing with sorafenib.
The research explored the mechanisms of CSS and its interaction with sorafenib in treating HCC. The effect on HCC cell proliferation was tested through an MTT assay, helping in the evaluation of CSS combined with sorafenib. To identify key gene targets of CSS in HCC, the researchers used LASSO-Cox regression and developed a three-gene signature model. They looked for correlations between immune cells, immune checkpoints, and the risk score to evaluate the influence of CSS on immunity. The binding interactions between the CSS components and the target genes were validated using molecular docking and Surface Plasmon Resonance assays.
The results revealed that CSS and sorafenib worked together to inhibit the growth of HCC cells. The researchers identified a network of ten core compounds and 224 targets by using a drug compound-target network. The predictive three-gene model targets (AKT1, MAPK3, and CASP3) indicated that heightened risk scores corresponded with cancer-promoting immune cells and elevated immune checkpoint protein expression. Validation of the strong binding affinity of CSS's active components to the target genes was achieved using molecular docking and Surface Plasmon Resonance. Western blot analysis affirmed that CSS indeed inhibited the expression of these gene targets when used simultaneously with sorafenib.
