Wang En-Yu, Wang Jing-Hui, Ding Rui, Li Zhong-Qiu, Zhai Meng-Ting, Ge Rui-Rui, Zhou Peng, Wang Liang, Huang Jin-Ling
Graduate School, Anhui University of Chinese Medicine Hefei 230012, China.
School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine Hefei 230012, China Anhui Province Key Laboratory of Chinese Medicinal Formula Hefei 230012, China.
Zhongguo Zhong Yao Za Zhi. 2020 Apr;45(8):1779-1788. doi: 10.19540/j.cnki.cjcmm.20200120.401.
To investigate the mechanism of Coptidis Rhizoma-Pinelliae Rhizoma in the treatment of gastric cancer based on syste-matic pharmacology and data mining. The chemical constituents of Coptidis Rhizoma and Pinelliae Rhizoma were obtained from Traditio-nal Chinese Medicine Systems Pharmacology Database(TCMSP) and Shanghai Institute of Organic Chemistry database of Chinese Academy of Sciences by data mining. Then the active ingredients were screened by ADME, and the targets of the active ingredients were predicted by chemometrics. Molecular docking and free energy analysis were used to verify and screen the targets, so as to obtain the therapeutic targets of Coptidis Rhizoma and Pinelliae Rhizoma for gastric cancer. The biological functions, diseases and related signal pathways corresponding to the targets were further analyzed, and then the multi-component, multi-target and multi-channel mechanism of Coptidis Rhizoma and Pinelliae Rhizoma for gastric cancer were elaborated. Finally, MTT, Scratch, Transwell and Western blot experiments were carried out to verify the inhibitory effect of Coptidis Rhizoma and Pinelliae Rhizoma on human gastric cancer cell line MKN-45. A total of 46 active ingredients of Coptidis Rhizoma and Pinelliae Rhizoma were screened, as well as 77 corresponding targets, 38 targets related to gastric cancer and its complications, top 8 related signaling pathways, and top 20 target molecular functions by GO analysis. Cell experiments also proved that Coptidis Rhizoma and Pinelliae Rhizoma could effectively inhibit the proliferation, invasion and migration ability of gastric cancer cells and inhibit TGF-β1-induced Wnt/β-catenin signaling pathway activation. Coptidis Rhizoma and Pinelliae Rhizoma drug pair has many active ingredients, which can regulate nervous and mental system, cell cycle, cell differentiation and metastasis, and enhance anti-inflammatory and immune functions, playing a synergistic anti-cancer role in gastric cancer and its complications and providing new ideas for the follow-up clinical treatment of gastric cancer.
基于系统药理学和数据挖掘研究黄连-半夏治疗胃癌的机制。通过数据挖掘从中药系统药理学数据库(TCMSP)和中国科学院上海有机化学研究所数据库获取黄连和半夏的化学成分。然后通过ADME筛选活性成分,并通过化学计量学预测活性成分的靶点。利用分子对接和自由能分析对靶点进行验证和筛选,以获得黄连和半夏治疗胃癌的靶点。进一步分析靶点对应的生物学功能、疾病及相关信号通路,阐述黄连和半夏治疗胃癌的多成分、多靶点、多途径机制。最后进行MTT、划痕、Transwell和蛋白质免疫印迹实验,验证黄连和半夏对人胃癌细胞系MKN-45的抑制作用。共筛选出黄连和半夏的46种活性成分,以及77个相应靶点、38个与胃癌及其并发症相关的靶点、前8条相关信号通路和通过基因本体(GO)分析得到的前20个靶标分子功能。细胞实验也证明,黄连和半夏可有效抑制胃癌细胞的增殖、侵袭和迁移能力,并抑制转化生长因子-β1(TGF-β1)诱导的Wnt/β-连环蛋白信号通路激活。黄连-半夏药对有多种活性成分,可调节神经和精神系统、细胞周期、细胞分化和转移,并增强抗炎和免疫功能,在胃癌及其并发症中发挥协同抗癌作用,为后续胃癌临床治疗提供新思路。