目的 基于网络药理学和靶向验证探讨木犀草素治疗结肠癌的作用机制。方法 基于网络药理学筛选木犀草素治疗结肠癌的潜在靶点，通过蛋白互作网络进一步筛选核心靶点，基于核心靶点进行京都基因与基因组百科全书（KEGG）分析，找到关键的作用通路；根据找到的关键靶点及通路进行在体结肠癌移植瘤模型的药理实验验证。采用ELISA试剂盒检测关键指标的水平，采用苏木精-伊红（HE）染色评价药物对肿瘤的病理学改变，采用免疫组织化学法及免疫印迹法检测肿瘤关键靶蛋白的表达。结果 木犀草素可能主要作用于白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）等靶点，影响Toll样受体（TLR）/髓样分化因子88（MyD88）/核因子-κB（NF-κB）信号通路起到治疗肿瘤的效果。实验验证结果显示，木犀草素显著降低了荷瘤小鼠机体的IL-6、IL-1β、TNF-α水平，改善了机体的氧化应激状态[提升超氧化物歧化酶（SOD）水平，降低丙二醛（MDA）水平]，抑制了TLR/MyD88/NF-κB信号通路的表达。结论 木犀草素具有显著的抗结肠癌效果，可能是通过降低机体炎症水平、改善氧化应激状态以及抑制TLR/MyD88/NF-κB通路表达实现的。

Objective To investigate the effect and mechanism of luteolin in treatment of colon cancer based on network pharmacology and targeted validation. Methods Potential targets of luteolin in treatment of colon cancer were screened based on network pharmacology, and the core targets were further screened by protein network interaction. KEGG analysis was performed based on the core targets to find the key pathways. According to the key targets and identified pathways, pharmacological experiments were carried out to verify in colon cancer model. ELISA kit was used to detect the content level of key indicators, HE staining was used to evaluate the pathological changes of the drug on the tumor. Immunohistochemistry and Western blotting were used to detect the expression of key target proteins of the tumor. Results Luteolin may mainly act on IL-6, IL-1β, TNF-α and affect TLR/MyD88/NF-κB signaling pathway to play a therapeutic effect on tumors. The experimental results showed that luteolin significantly reduced the level of IL-6, IL-1β, TNF-α, and improved the oxidative stress state (increasing SOD level, decreasing MDA level), and inhibited the expression of TLR/MyD88/NF-κB signaling pathway in tumor mice. Conclusion Luteolin has a significant anti-tumor effect on colon cancer, which may be achieved by reducing the level of inflammation, improving oxidative stress, and inhibiting TLR/MyD88/NF-κB.

R285

河南省医学科技攻关计划项目（2018020135）