基于生物信息学的益肾通癃胶囊治疗前列腺癌药效机制及其验证研究

Study on the pharmacodynamic mechanism and validation of Yishen Tonglong Capsules in the treatment of prostate cancer based on bioinformatics

目的:采用生物信息学研究益肾通癃胶囊治疗前列腺癌的药效机制,并借助细胞实验验证。方法:借助TCMSP、TCMID、GeneCards等数据库及相关文献检索益肾通癃胶囊及前列腺癌的作用靶点,构建益肾通癃胶囊治疗前列腺癌的药物-疾病-靶点网络及蛋白-蛋白相互作用网络,进行KEGG信号通路富集分析,并以细胞实验进一步验证相关靶基因。结果:共获取益肾通癃胶囊33个主要有效成分,278个作用靶点,3331个前列腺癌靶点,益肾通癃胶囊治疗前列腺癌共涉及185个共同靶点;KEGG通路富集分析提示益肾通癃胶囊治疗前列腺癌主要集中在肿瘤信号通路、MicroRNA调控、磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)、丝裂原活化蛋白激酶(MAPK)、p53肿瘤抑制、肿瘤坏死因子(TNF)、血管内皮生长因子(VEGF)等与细胞凋亡、细胞周期密切相关的信号通路。与空白血清组比较,益肾通癃胶囊低、中、高剂量组显著抑制前列腺癌DU-145细胞的增殖并促进其凋亡(P<0.05),同时能够将细胞周期阻滞在G0/G1期;与空白血清组比较,益肾通癃胶囊各剂量组Bax、Bcl-2、Ced-4、CDK4、CDK6、cyclin E1蛋白表达水平显著降低(P<0.05),cyclin D1蛋白表达水平显著升高(P<0.05)。结论:益肾通癃胶囊治疗前列腺癌的药效机制,可能与其调控细胞增殖、凋亡和细胞周期的信号通路相关。

Objective: To study the pharmacodynamic mechanism of Yishen Tonglong Capsules in the treatment of prostate cancer by bioinformatics, and to verify it with the help of cell experiments. Methods: With the help of TCMSP, TCMID,GeneCards and other databases and related literatures, Yishen Tonglong Capsules and their targets in prostate cancer were searched, and the drug-disease-target network and protein-protein interaction of Yishen Tonglong Capsules in the treatment of prostate cancer were constructed. Network, carry out KEGG signaling pathway enrichment analysis, and further verify related target genes with cell experiments. Results: A total of 33 active ingredients, 278 targets, and 3 331 targets for prostate cancer were obtained from Yishen Tonglong Capsules, and a total of 185 common targets were involved in the treatment of prostate cancer by Yishen Tonglong Capsules;KEGG pathway enrichment analysis indicated that Yishen Tonglong Capsules in the treatment of prostate cancer mainly focus on tumor signaling pathways, MicroRNA regulation, phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT), mitogen-activated protein kinase(MAPK), p53 tumor inhibition, tumor Necrosis factor(TNF), vascular endothelial growth factor(VEGF) and other signaling pathways closely related to apoptosis and cell cycle. Compared with blank serum group,Yishen Tonglong Capsules low-dose, medium-dose and high-dose groups significantly inhibited the proliferation of prostate cancer DU-145 cells and promoted their apoptosis(P<0.05), and could block the cell cycle at G0/G1. Compared with the blank serum group, the protein expression levels of Bax, Bcl-2, Ced-4, CDK4, CDK6, and cyclin E1 in each dose group of Yishen Tonglong Capsules were significantly decreased(P<0.05), and the protein expression level of cyclin D1 was significantly increased(P<0.05).Conclusion: The pharmacodynamic mechanism of Yishen Tonglong Capsules in the treatment of prostate cancer may be related to the signaling pathways regulating cell proliferation, apoptosis and cell cycle.