Hepatocellular carcinoma (HCC) is the most common primary malignant liver cancer and a leading cause of cancer-related deaths worldwide. Camptothecin (CPT), a cytotoxic alkaloid, inhibits cancer cell replication by blocking DNA topoisomerase 1. This study is to investigate the role and mechanism of CPT in HCC using network pharmacology, molecular docking, and experiments. Cell vitality and cell proliferation were examined using Cell counting Kit-8 (CCK8) and colony assay. Cell cycle and apoptosis were tested using flow cytometry. Cell migration and invasion were detected using wound healing and transwell assays, respectively. Molecular interaction networks and pathways affected by CPT in HCC were analyzed using network pharmacology and bioinformatics analysis. Additionally, molecular docking was utilized to predict the interaction between CPT and matrix metalloproteinase 9 (MMP9). Protein levels were examined using western blot. MMP9 levels in liver hepatocellular carcinoma (LIHC) tissues and relationship between MMP9 expression and overall survival of patients with HCC were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA). Relationship between MMP9 and clinical characteristics of HCC was predicted using the Universal Adverse Outcome Pathway (UALCAN) database. Animal models were constructed to analyze the role of CPT and MMP9. HCC cell viability was hindered with an increase of CPT content. CPT repressed HCC cell proliferation, migration, and invasion and promoted cell apoptosis. CPT hinders HCC via regulating multiple pathways, and MMP9 may be a potential core target of CPT in HCC. Besides, MMP9 expression was increased in HCC tissues and cells. MMP9 overexpression promoted HCC cell biological functions. CPT inhibited HCC progression by regulating MMP9 expression in vitro and in vivo . CPT inhibits HCC progression via targeting MMP9. Camptothecin hinders HCC progression through inhibiting MMP9. • CPT inhibits HCC cell malignant behaviors. • MMP9 is a potential therapeutic target in HCC. • In HCC cells, MMP9 levels were highly expressed. • MMP9 up-regulation facilitates HCC cell malignant behaviors. • CPT alleviates HCC progression via targeting MMP9.
Li et al. (Sun,) studied this question.