Exploring the potential mechanism of Chouchunpi San in the treatment of colorectal cancer based on network pharmacology and experimental research
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摘要:
目的：基于网络药理学和细胞实验探讨中药复方臭椿皮散（Chouchunpi San，CCPS）治疗结直肠癌的潜在机制。方法：通过网络药理学筛选臭椿皮散作用靶点和结直肠癌靶点，构建蛋白质互作（protein-protein interaction networks，PPI）网络，预测臭椿皮散可能的作用靶点，通过富集分析预测臭椿皮散抗结直肠癌的作用途径；CCK-8法检测臭椿皮散对结直肠癌细胞活性的影响；使用不同浓度臭椿皮散处理结直肠癌细胞，流式实验检测细胞凋亡情况；划痕实验检测结直肠癌细胞迁移能力； Western blot检测STAT3蛋白的表达。结果：通过多个数据库检索到臭椿皮散的117个活性成分，920个潜在靶点，787个药物与疾病交集靶点。PPI网络分析得到STAT3、MAPK1、AKT1、MYC等核心靶点，GO功能富集和KEGG通路分析结果显示臭椿皮散主要参与对细胞凋亡、氧化应激反应等生物学过程，参与的通路涉及癌症通路，如AGE-RAGE信号通路、PI3K-Akt信号通路等。分子对接结果显示STAT3与其对应的化合物licochalcone A有较好的结合能力。细胞实验显示臭椿皮散抑制结直肠癌细胞活性，降低细胞迁移能力，促进结直肠癌细胞凋亡。Western blot结果显示，经不同浓度臭椿皮散处理后，细胞中STAT3蛋白表达显著下降，且呈浓度依赖性。结论：臭椿皮散治疗结直肠癌具有多成分、多靶点、多通路的作用机制，臭椿皮散明显抑制结直肠癌细胞的活性及迁移能力，其作用机制可能与靶向降低STAT3蛋白水平有关。
Abstract:
Objective：To explore the potential mechanisms of Chouchunpi San（CCPS）on colorectal cancer based on cell experiments and network pharmacology. Methods：The targets of CCPS active compounds and colorectal cancer were screened by network pharmacology. The protein-protein interaction（PPI）network were constructed，and the potential targets of CCPS were predicted. Enrichment analysis was conducted to predict pathways through which CCPS may exert its anti-colorectal cancer effects. The effect of CCPS on the viability of colorectal cancer cells was detected by CCK-8 assay，and the effects of different concentrations of CCPS on apoptosis of colorectal cancer cells were detected by flow cytometry. Wounding-healing assay was employed to investigate the impact of CCPS on the migration capacity of colorectal cancer cells. The expression of STAT3 protein in colorectal cancer cells after CCPS induction was determined by Western blot. Results：There are 117 active components，920 potential targets，and 787 drug and disease intersection targets of CCPS were retrieved through the database. Protein-protein interaction（PPI）network analysis identified core targets such as STAT3，MAPK1，AKT1，and MYC.The results of GO enrichment and KEGG pathway analysis indicated that CCPS in mainly involved in biological processes relalted to cell apoptosis and oxidative stress response，and the pathways involved included cancer pathway，AGE-RAGE signaling pathway，and PI3K-Akt signaling pathway.Molecular docking results showed that STAT3 had a highly binding affinity with its core compound licochalcone A. Cell experiments demonstrated that CCPS inhibited the proliferation and migration capacity of colorectal cancer cells and significantly promoted cell apoptosis. Western blot results showed that the expression of STAT3 protein in cells significantly decreased after treatment with different concentrations of CCPS，and the decrease was concentration-dependent. Conclusion：This study revealed the multi-component，multi-target，and multi-pathway mechanisms of CCPS in the treatment of colorectal cancer. CCPS significantly inhibited the proliferation and migration capacity of colorectal cancer cells and its mechanism may be related to the targeted reduction of STAT3 protein levels.
