目的 采用网络药理学探究小陷胸汤治疗大肠癌的作用机制。方法 通过中药系统药理学数据库及分析平台（TCMSP），对组成小陷胸汤的3个单味药半夏、瓜蒌和黄连分别进行活性成分的收集和筛选，构建成分-靶点网络图，同时采用GeneCards数据库获取大肠癌疾病靶点。应用Cytoscape软件，采用蛋白互作的方式，垂钓小陷胸汤治疗大肠癌的核心靶点，并采用ClueGo对核心靶点进行基因本体（gene ontology，GO）和通路的富集分析。采用PyRx软件对核心成分及蛋白靶点进行分子对接，对网络药理学的研究结果进行验证。结果 筛选得到32个小陷胸汤治疗大肠癌的活性成分，181个对应的蛋白靶点及9329个大肠癌疾病靶点。通过靶点垂钓的方式，得到360个小陷胸汤治疗大肠癌的核心靶点。GO富集分析发现，小陷胸汤治疗大肠癌在生物过程（biological process，BP）方面，与烟酰胺腺嘌呤二核苷酸（nicotinamide adenine dinucleotide，NAD）依赖性组蛋白脱乙酰酶活性、消旋酶活性负调控、胆囊收缩素反应、调节脱氧核糖核酸酶活性等有关；分子功能（molecular function，MF）方面，与蛋白质丝氨酸/苏氨酸激酶活性、蛋白质丝氨酸/苏氨酸激酶活性调节、腺嘌呤核苷三磷酸（adenosine-triphosphate，ATP）结合、凋亡过程中半胱氨酸型内肽酶活性调节等有关；在细胞组成（cellular component，CC）方面，主要与纺锤体微管、组蛋白脱乙酰酶复合物、核小体、ESC/E（Z）复合物有关。信号通路富集分析注释得到胃泌素信号、细胞周期、乙型肝炎感染、DNA损伤反应4个相关通路。分子对接结果表明由小陷胸汤中筛选出的活性成分与对应的蛋白靶点具有良好的结合能力。结论 小陷胸汤通过调控胃泌素信号通路、细胞周期通路、乙型肝炎感染通路、DNA损伤反应通路治疗大肠癌。

Objective To explore the mechanism of Xiaoxianxiong Decoction (小陷胸汤) on colorectal cancer by network pharmacology. Methods The active components of Banxia (Pinelliae Rhizoma), Gualou (Trichosanthis Fructus) and Huanglian (Coptidis Rhizoma) in Xiaoxianxiong Decoction were collected and screened by TCMSP, and component-target network was constructed, GeneCards database was used to obtain colorectal cancer disease targets. Cytoscape software was used to identify the targets of Xiaoxianxiong Decoction in the treatment of colorectal cancer, and ClueGo was used to perform gene ontology (GO) and pathway enrichment analysis. Components and protein targets were docked by PyRx software to verify the accuracy. Results Thirty-two active components of Xiaoxianxiong Decoction in the treatment of colorectal cancer, 181 corresponding protein targets and 9329 colorectal cancer disease targets were screened. By target fishing, 360 Hub targets of Xiaoxianxiong Decoction were obtained. GO enrichment analysis showed the biological process (BP) of Xiaoxianxiong Decoction in the treatment of colorectal cancer was related to NAD-dependent histone deacetylase activity, negative regulation of helioase activity, regulation of deoxyribonuclease activity, response to cholecystokinin, regulation of protein neddylation and so on. Molecular function (MF) was related to protein serine/threonine kinase activity, regulation of protein serine/threonine kinase activity, adenosine-triphosphate(ATP) binding, regulation of cysteine-type endopeptidase activity involved in apoptotic process and sequence-specific double-stranded DNA binding. Cellular component (CC) was related to spindle microtubule, histone deacetylase complex, nuclear nucleosome and ESC/E(Z) complex. The enrichment analysis of signal pathways showed that they were related with gastrain signaling pathway, cell cycle pathway, hepatitis B infection pathway and DNA damage response pathway. Molecular docking results showed that the active components screened from Xiaoxianxiong Decoction had good binding ability to the corresponding protein targets. Conclusion Xiaoxianxiong Decoction can treat colorectal cancer by regulating gastrain signaling pathway, cell cycle pathway, hepatitis B infection pathway and DNA damage response pathway.

R285.5

黑龙江省自然科学基金资助项目（LH2021H002）；2021年哈尔滨商业大学教师“创新”项目支持计划项目（LH2021H002）；中央支持地方高校改革发展基金优秀青年人才项目（2020YQ12）；黑龙江省卫生计生委科技计划（2017-132）；黑龙江省教育厅面上项目（12541571）