Pharmacological Effects of a Ginseng-Containing Chinese Medicine Formula in Treating Hepatocellular Carcinoma Based on Comprehensive Bioinformatics and Experimental Validation.

Gao, Tianqi; Zhou, Ruisheng; Huang, Dan; Wu, Dailin; Gao, Yong; Yuan, Yi; Li, Jing; Huang, Shangyi; Xian, Yanfang; Tang, Ying; Lin, Zhixiu; Zhou, Daihan; Wang, Shutang

Ginseng-containing Shentao Ruangan granules (STR) have been a well-known Chinese medicine prescription for the treatment of hepatocellular carcinoma (HCC) in China for decades. This study aimed to establish an in silico experimental framework to decipher the underlying mechanism of STR in the treatment of HCC. Microarray analysis, network pharmacology, RNA-sequencing (RNA-seq), bioinformatics analysis, and in vivo and in vitro experiments were used as integrated approaches to uncover the effects and mechanisms of action of STR. The introduction of STR significantly suppresses the proliferation and metastasis of HepG2 and Huh7 cells. STR treatment notably suppressed the growth of transplanted Huh7 tumors. Furthermore, STR administration reduced the expression of various epithelial-to-mesenchymal transition (EMT)-related proteins including N-cadherin, vimentin, and β -catenin. By employing a systems biology approach, 21 common genes were identified across RNA-seq data, TCGA-HCC dataset, and network pharmacology analysis. Finally, of these genes nine were found to be associated with both OS and PFS in patients with HCC within the TCGA cohort. Validation of candidate genes by qPCR and WB identified a significant downregulation in the expression of pGSK3 β and RELA protein with increasing concentrations of STR. These results elucidated the mechanism by which STR inhibits tumor growth and EMT of HCC may be related to the GSK3 β /RELA pathway.

THERAPEUTIC use of ginseng; CHINESE medicine; IN vitro studies; NF-kappa B; CELL migration; EPITHELIAL-mesenchymal transition; PHARMACEUTICAL chemistry; CELL proliferation; POLYMERASE chain reaction; TREATMENT effectiveness; IN vivo studies; DESCRIPTIVE statistics; XENOGRAFTS; CELLULAR signal transduction; BIOINFORMATICS; METASTASIS; CELL lines; CELL culture; MICROARRAY technology; WESTERN immunoblotting; MICROBIOLOGICAL assay; ONE-way analysis of variance; ANALYSIS of variance; GINSENG; DATA analysis software; HEPATOCELLULAR carcinoma; SEQUENCE analysis

American Journal of Chinese Medicine, 2024, Vol 52, Issue 8, p2511

0192-415X

Academic Journal

10.1142/S0192415X24500964