目的 采用網(wǎng)絡(luò)藥理學(xué)、分子對接及實驗驗證的方法，探討吳茱萸治療結(jié)直腸癌的作用機制。方法 運用中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫與分析平臺（TCMSP）數(shù)據(jù)庫及查閱國內(nèi)外相關(guān)文獻收集吳茱萸活性成分，通過GeneCards、OMIM、TTD數(shù)據(jù)庫收集結(jié)直腸癌靶點，將成分-疾病靶點取交集后進行基因本體（GO）注釋及京都基因與基因組百科全書（KEGG）通路富集分析。AutoDock vina對核心成分與核心靶點進行分子對接。通過細胞增殖與活性檢測-8（CCK-8）法和流式細胞儀檢測異鼠李素對SW480細胞增殖和凋亡的影響；通過蛋白免疫印跡法（Western blotting法）檢測細胞中腫瘤蛋白p53 （TP53）、絲氨酸/蘇氨酸蛋白激酶1 （AKT₁）、血管內(nèi)皮生長因子A （VEGFA）的蛋白表達情況。結(jié)果 吳茱萸30個活性成分對應(yīng)174個靶點，結(jié)直腸癌對應(yīng)1 484個靶點，二者取交集獲得98個靶點，GO涉及細胞增殖、細胞凋亡等生物過程，KEGG富集為癌癥通路、PI3K/AKT等信號通路，分子對接結(jié)果顯示異鼠李素與TP53、AKT₁和VEGFA親和力良好。與對照組比較，異鼠李素可抑制SW480細胞增殖，促進細胞凋亡；與對照組比較，異鼠李素下調(diào)了AKT₁和VEGFA的蛋白表達水平（P＜0.01），上調(diào)TP53的蛋白表達水平（P＜0.01）。結(jié)論 吳茱萸治療結(jié)直腸癌可通過多成分、多靶點、多通路途徑來發(fā)揮作用，其中異鼠李素是主要活性成分。

Objective To investigate the mechanism of Evodia rutaecarpa in treatment of colorectal cancer based on network pharmacology, molecular docking and experimental verification. Methods The active ingredients of E. rutaecarpa were collected by TCMSP and relevant domestic and foreign literature, targets to colorectal cancer were collected through GeneCards, OMIM and TTD databases. The component-disease intersection targets were analyzed through GO and KEGG analysis. AutoDock vina was used to molecular docking between the core components and the core targets. The effects of isorhamnetin on proliferation and apoptosis of SW480 cells by cell counting kit-8 (CCK-8) and flow cytometry. Western blotting was employed to determine the expression levels of TP53,AKT₁ and VEGFA. Results The 30 active components of E. rutaecarpa corresponding to 174 targets, 1 484 corresponding targets for colorectal cancer, and 98 targets for the intersection of the two. GO involve biological processes such as cell proliferation, apoptosis and so on. KEGG enrichment pathways involve cancer pathway,PI3K-Akt signaling pathway. Molecular docking results showed that isorhamnetin had a good affinity with TP53, AKT₁, VEGFA. Isorhamnetin can inhibit proliferation of SW480 cell and and promote apoptosis compared with the group. Compared with the control group, isorhamnetin down-regulated the expression of AKT₁and VEGFA (P＜0.01) and up-regulated the expression of TP53 (P＜0.01). Conclusion E. rutaecarpa can play a role in treatment of colorectal cancer through multi-component, multi-target and multi-pathway pathways, and isorhamnetin is the main active ingredient.

R285.5