Compound kushen injection synergises with sorafenib to improve response in advanced hepatocellular carcinoma

Abstract

Abstract: Objective:Clinical cohort, network pharmacological framework and molecular docking techniques were used to elucidate the material basis and molecular mechanism of compound compound kushen injection (CKI) synergising with sorafenib in the treatment of advanced hepatocellular carcinoma (HCC).
Methods:A total of 134 patients with advanced HCC treated in our hospital between July 2019 and June 2022, including 67 patients in the CKI-sorafenib group and 67 patients in the sorafenib group, were selected to analyse the response rate and overall survival rate of patients in both groups. The CKI anti-advanced HCC target genes were identified by a web-based pharmacological framework combined with the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform and GeneCards,OMIM,PharmGkb,TTD or DrugBank databases. The expression of FBJ murine osteosarcoma viral oncogene homolog (FOS) and epidermal growth factor receptor (EGFR) was verified by enzyme-linked immunosorbent assay before and after treatment in both groups.
Results:The treatment response rate and survival rate of patients in the CKI-sorafenib group were higher than those in the sorafenib group (response rate:74.6% vs. 66.2%, P=0.032; survival rate:38.8% vs. 23.9%, P=0.013).FOS and EGFR are the core target genes of CKI against advanced HCC. After 3 months of treatment, peripheral blood FOS and EGFR concentrations were significantly lower in patients in the CKI-sorafenib group compared with those in the sorafenib group (FOS: (8.41±2.17) ng/ml vs. (9.85±2.47) ng/ml, P<0.001; EGFR: (5.47±2.14) ng/ml vs. (6.28±2.04) ng/ml, P=0.027)]. Molecular docking modelling fraction confirmed that quercetin could interact with FOS and EGFR with binding energies of -8.2 kcal/mol and -7.9 kcal/mol, respectively. Conclusion:CKIs synergise with sorafenib to increase response rates and improve survival time in patients with advanced HCC, with FOS and EGFR as potential mechanisms mediating their response.

Key words: Advanced hepatocellular carcinoma, Compound kushen injection, Network pharmacology, Molecular docking, Sorafenib

Li Xianchen, Xu Qiuyan, Sheng Wenfei, Li Dongliang, Wu Qingqing, Tao Zhongyi. Compound kushen injection synergises with sorafenib to improve response in advanced hepatocellular carcinoma[J]. Electronic Journal of Liver Tumor, 2023, 10(4): 42-50.

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