Abstract

This bioinformatics study aimed to characterize and certify crucial anti-cancer targets, functional processes, and molecular mechanisms of Pachyman in treating hepatocellular carcinoma (HCC) by using pharmacology network and molecular docking analyses, by experimental validation. The crucial anti-HCC targets of Pachyman, including ALB, VEGFA, TNF, CASP3, SRC, EGF, CXCR4, STAT3, HRAS, HSP90AA1, MMP9, BCL2L1, FGF2, and PTPRC, were identified. In addition, the correlative networks of all crucial biotargets of Pachyman in treating HCC were created accordingly. Functionally, these crucial genes were correlated using angiogenesis and neoplastic metastasis of HCC. Interestingly, the molecular docking findings indicated that ALB and VEGFA in HCC might be potent pharmacological targets of Pachyman. In experimental validation, the clinical samples of HCC showed reduced ALB protein expression and increased VEGFA protein level. Following Pachyman treatments in vitro, the intracellular level of ALB protein was elevated, whereas the cellular content of VEGFA protein was downregulated. Taken together, current bioinformatics findings based on pharmacology network and molecular docking analyses elucidate the detailed molecular targets and signaling mechanisms of Pachyman in treating HCC. Interestingly, validated biotargets of ALB and VEGFA may be main potential biomarkers for detecting HCC medically.

Highlights

  • Hepatocellular carcinoma (HCC) refers to a malignant tumor, occurring in liver tissue in situ

  • As shown in the Venn diagram (Figure 1), the data reported a total of 16,763 hepatocellular carcinoma (HCC)-associated genes and 166 Pachymanassociated genes

  • The topological data indicated a close relevance among the intersection genes, characterized in the protein–protein interaction (PPI) network map (Figure 2A)

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Summary

Introduction

Hepatocellular carcinoma (HCC) refers to a malignant tumor, occurring in liver tissue in situ. Well-evidenced anti-cancer benefits have been found, there are still only few studies regarding the pharmacological effects of Pachyman in treating HCC. An attractive strategy using network pharmacology and molecular docking analyses can function as an emerging and promising tool for revealing detailed biotargets and molecular mechanisms of candidate natural agents for treating medical diseases (Li et al, 2020a; Li et al, 2021a), including liver disease (Su et al, 2019), coronavirus disease 2019 (COVID-19) (Qin et al, 2021), and meningitis (Li et al, 2021b). The present study was designed to optimize network pharmacology and molecular docking methods in identifying the bioinformatics findings of Pachyman in treating HCC, including detailed biological targets, functional processes, and signaling pathways. Some bioinformatics data were validated for potential clinical use of Pachyman in treating HCC in future

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