Exploring the potential targets of Sanshimao formula for hepatocellular carcinoma treatment by a method of network pharmacology combined with molecular biology

Qin Yu; Zhe Chen; Minglin Liu; Yongbin Meng; Xiaoyan Li; Bai Li; Juan Du

doi:10.1016/j.jep.2022.115531

Exploring the potential targets of Sanshimao formula for hepatocellular carcinoma treatment by a method of network pharmacology combined with molecular biology

J Ethnopharmacol. 2022 Oct 28:297:115531. doi: 10.1016/j.jep.2022.115531. Epub 2022 Jul 15.

Authors

Qin Yu¹, Zhe Chen², Minglin Liu³, Yongbin Meng³, Xiaoyan Li³, Bai Li⁴, Juan Du⁵

Affiliations

¹ Department of Traditional Chinese Medicine, the First Affiliated Hospital of Naval Military Medical University, Shanghai, China; Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² Department of Rehabilitation Medicine, the First Affiliated Hospital of Naval Military Medical University, Shanghai, China.
³ Department of Traditional Chinese Medicine, the First Affiliated Hospital of Naval Military Medical University, Shanghai, China.
⁴ Department of Rehabilitation Medicine, the First Affiliated Hospital of Naval Military Medical University, Shanghai, China. Electronic address: libai9@126.com.
⁵ Department of Traditional Chinese Medicine, the First Affiliated Hospital of Naval Military Medical University, Shanghai, China. Electronic address: dujuan714@163.com.

PMID: 35840058
DOI: 10.1016/j.jep.2022.115531

Abstract

Ethnopharmacological relevance: The Sanshimao (SSM) formula is an effective prescription for hepatocellular carcinoma (HCC) therapy in the clinical setting. This prescription is made up of four herbals, Maorenshen, Shijianchuan, Shishangbai and Shidachuan, which are used for detoxification and removing blood stasis. However, its mechanism in the treatment of HCC remains ambiguous.

Aim of the study: To explore the potential targets of SSM against HCC by network pharmacology analysis and verify the data using molecular biological methods.

Materials and methods: We screened active components and potential targets by data mining, constructed a network, and performed functional analysis and pathway enrichment to explore the therapeutic targets of SSM for HCC treatment. Then, the effects of SSM on HCC cells were studied to validate the data from network pharmacology analysis.

Results: Eighty-eight common targets were obtained by mapping 932 HCC-related genes, and 325 targets corresponded to 11 active components of SSM. They were enriched in various biological processes, such as the response to inorganic substances, response to toxic substances and apoptotic signalling pathway, and multi-pathways involved pathways in cancer, EGFR tyrosine kinase inhibitor resistance, and AGE-RAGE signalling pathway in diabetic complications, as evaluated by the analysis of advanced functions and pathways. TP53, JUN, HSP90AA1, EGFR, AR and MAPK1 might be the core targets closely related to the effects of SSM on HCC according to PPI analysis. Treatment with SSM decreased cell viability and migration, promoted apoptosis and inhibited the EGFR/FAK/AKT signalling pathway.

Conclusion: This research preliminarily indicates that SSM treats HCC via multiple components and pathways. EGFR/FAK/AKT are promising therapeutic targets of SSM for HCC treatment. This provides objective evidence for further mechanistic research and the future development and clinical application of SSM in HCC patients.

Keywords: EGFR; HCC; Network pharmacology; Sanshimao formula.

MeSH terms

Carcinoma, Hepatocellular* / metabolism
Drugs, Chinese Herbal* / pharmacology
Drugs, Chinese Herbal* / therapeutic use
ErbB Receptors
Humans
Liver Neoplasms* / drug therapy
Liver Neoplasms* / genetics
Liver Neoplasms* / metabolism
Molecular Biology
Molecular Docking Simulation
Network Pharmacology
Proto-Oncogene Proteins c-akt

Substances

Drugs, Chinese Herbal
ErbB Receptors
Proto-Oncogene Proteins c-akt