目的 利用網(wǎng)絡(luò)藥理學(xué)和分子對(duì)接的方法研究西黃丸治療宮頸癌的分子機(jī)制。方法 采用計(jì)算機(jī)檢索TCMSP、BATMAN-TCM數(shù)據(jù)庫(kù)，并篩選西黃丸的有效活性成分及作用靶點(diǎn)。檢索OMIM、GeneCards數(shù)據(jù)庫(kù)，獲得宮頸癌的疾病靶點(diǎn)，合并去重后，與西黃丸獲得的有效成分靶點(diǎn)取交集。運(yùn)用String數(shù)據(jù)庫(kù)構(gòu)建蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)圖。利用Cytoscape 3.9.1軟件進(jìn)行可視化，并采用DAVID數(shù)據(jù)庫(kù)對(duì)交集基因進(jìn)行（GO）功能富集分析和京都基因與基因組百科全書(shū)（KEGG）通路富集分析。最后運(yùn)用AutoDock Vina、Pymol軟件進(jìn)行分子對(duì)接驗(yàn)證。結(jié)果 篩選得到西黃丸70個(gè)主要活性成分，包括表雄酮、槲皮素、雄甾酮等。與宮頸癌相關(guān)的靶點(diǎn)有116個(gè)，核心靶點(diǎn)有腫瘤蛋白P53（TP53）、表皮生長(zhǎng)因子受體（EGFR）、蛋白激酶B1（Akt1）、白細(xì)胞介素（IL）-6、原癌基因（MYC）、轉(zhuǎn)錄因子AP-1（JUN）、半胱氨酸蛋白酶3（CASP3）、IL-1B、腫瘤壞死因子（TNF）、雌激素受體1（ESR1）、B淋巴細(xì)胞2（Bcl-2）、低氧誘導(dǎo)因子-1A（HIF-1A）、基質(zhì)金屬蛋白酶9（MMP9）、V-Rel網(wǎng)狀內(nèi)皮增生病毒癌基因同源物A（RELA）等。GO和KEGG分析結(jié)果顯示，西黃丸治療宮頸癌的重要通路有IL-17、TNF、磷脂酰肌醇3-激酶（PI3K）/Akt、p53、HIF-1等信號(hào)通路。分子對(duì)接結(jié)果顯示：西黃丸的主要成分與核心靶點(diǎn)有良好的對(duì)接效果。結(jié)論 西黃丸主要通過(guò)調(diào)節(jié)IL-17、TNF、PI3K/Akt、p53，HIF-1等信號(hào)通路治療宮頸癌。

Objective To explore the mechanism of Xihuang Pills in treatment of cervical cancer through pharmacology network and molecular docking methods. Methods To search the active ingredients and targets of Xihuang Pills by TCMSP and BATMAN-TCM databases. To obtain the disease targets of cervical cancer OMIM and GeneCards databases. After the combination and deduplication, it intersected with the effective ingredient target obtained by Xihuang Pills. The protein interaction (PPI) network map was constructed using String database. Cytoscape 3.9.1 software was used for visualization, and the intersection genes were analyzed using DAVID database for functional enrichment (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Finally, AutoDock Vina and Pymol software were used to verify the molecular docking. Results Seventy main active components of Xihuang Pills were screened, including 3beta-hydroxy-5alpha-androstan-17-one, quercetin, androsterone, etc. There are 116 targets associated with cervical cancer, the core targets are TP53, EGFR, Akt1, IL-6, MYC, JUN, CASP3, IL-1B, TNF, ESR1, Bcl-2, HIF-1A, MMP9, RELA, etc. GO and KEGG analysis results showed that the important pathways of Xihuang Pills in treatment of cervical cancer were IL-17, TNF, PI3K/Akt, p53, HIF-1, and other signaling pathways. Conclusion Xihuang Pills mainly treats cervical cancer by regulating IL17, TNF, PI3K/Akt, p53, HIF-1 signaling pathways.

R285

南京中醫(yī)藥大學(xué)自然科學(xué)基金項(xiàng)目（XZR2021029）