School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Genes (Basel). 2024 Sep 29;15(10):1278. doi: 10.3390/genes15101278.
Compound Ku-Shen Injection (CKI) is a traditional Chinese medicine preparation derived from Ku-Shen and Bai-Tu-Ling, commonly used in the adjunctive treatment of advanced cancers, including liver cancer. However, the underlying mechanisms of CKI's effectiveness in cancer treatment are not well defined.
This study employs network pharmacology to investigate the traditional Chinese medicine (TCM) compatibility theory underlying CKI's action in treating liver cancer, with findings substantiated by molecular docking and in vitro experiments. Sixteen active components were identified from CKI, along with 193 potential targets for treating liver cancer. Key therapeutic target proteins, including EGFR and ESR1, were also identified. KEGG enrichment results showed that the neuroactive ligand-receptor interaction, cAMP signaling pathway, and serotonergic synapses make up the key pathway of CKI in the treatment of liver cancer. Molecular docking results confirmed that the key active ingredients effectively bind to the core targets. CCK-8 cytotoxic experiment results show that the CKI key components of oxymatrine and matrine can inhibit the growth of HepG2 liver cancer cell proliferation. A Western blot analysis revealed that oxymatrine suppresses the expression of EGFR, contributing to its therapeutic efficacy against liver cancer.
our study elucidated the therapeutic mechanism of CKI in treating liver cancer and unveiled the underlying principles of its TCM compatibility through its mode of action.
复方苦参注射液(CKI)是一种从苦参和白头翁中提取的中药制剂,常用于辅助治疗晚期癌症,包括肝癌。然而,CKI 治疗癌症的有效性的潜在机制尚不清楚。
本研究采用网络药理学方法探讨 CKI 治疗肝癌的中药配伍理论,并通过分子对接和体外实验进行验证。从 CKI 中鉴定出 16 种活性成分,以及 193 种治疗肝癌的潜在靶点。还确定了关键治疗靶蛋白,包括 EGFR 和 ESR1。KEGG 富集结果表明,神经活性配体-受体相互作用、cAMP 信号通路和 5-羟色胺能突触构成了 CKI 治疗肝癌的关键途径。分子对接结果证实,关键活性成分有效结合核心靶点。CCK-8 细胞毒性实验结果表明,苦参碱和氧化苦参碱等 CKI 关键成分可抑制 HepG2 肝癌细胞增殖。Western blot 分析表明,氧化苦参碱抑制 EGFR 的表达,从而发挥其治疗肝癌的疗效。
本研究阐明了 CKI 治疗肝癌的治疗机制,并通过其作用模式揭示了其中药配伍的潜在原理。