Mechanisms of Compound Kushen Injection for the treatment of bladder cancer based on bioinformatics and network pharmacology with experimental validation

Abstract

Background: Bladder cancer is the most common malignant neoplasm of the urinary system. Compound Kushen injection (CKI) is a Chinese medicinal preparation that has been used clinically to treat various types of cancers for more than 20 years. However, the pharmacological effect of CKI on bladder cancer requires further clarification.Methods: Network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI is effective against bladder cancer was further verified in vitro using the human bladder cancer cell line T24.Results: Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data mining revealed 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerts anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI has a therapeutic effect on bladder cancer by synergistically regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI could inhibit proliferation and migration of T24 bladder cancer cells, and induce their apoptosis. Moreover, RT-qPCR and western blot results indicated that CKI may treat bladder cancer by downregulating gene and protein expression levels, respectively of MMP-9, JUN, EGFR, and ERK1.Conclusions: CKI can inhibit proliferation and migration, and induce apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also has significant effects on regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.

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