目的 通過網(wǎng)絡(luò)藥理學(xué)及分子對接探索柴胡皂苷d治療鼻咽癌的作用機(jī)制。方法 通過SwissTargetPrediction、Stitch、GeneCards數(shù)據(jù)庫預(yù)測柴胡皂苷d藥物潛在的作用靶點，檢索DrugBank、GeneCards、TTD、Omim、Pharmgkb數(shù)據(jù)庫獲得鼻咽癌靶點；使用R 4.3.1軟件獲取柴胡皂苷d和鼻咽癌的交集靶點。運用STRING數(shù)據(jù)庫構(gòu)建交集靶點的蛋白相互作用（PPI）網(wǎng)絡(luò)；使用Cytoscape軟件對STRING數(shù)據(jù)庫篩選的靶點進(jìn)一步篩選核心靶點；使用R 4.3.1軟件“ClusterProfiler”包對柴胡皂苷d和鼻咽癌的交集靶點進(jìn)行基因本體（GO）富集分析和京都基因與基因組百科全書（KEGG）通路富集分析，通過分子對接明確柴胡皂苷d治療鼻咽癌的作用機(jī)制。結(jié)果 預(yù)測得到柴胡皂苷d靶點140個，篩選、去重得到鼻咽癌疾病靶點2 854個，最后得到交集靶點74個，得到信號轉(zhuǎn)導(dǎo)及轉(zhuǎn)錄激活因子3（STAT3）、絲裂原活化蛋白激酶1（MAPK1）、腫瘤蛋白p53（TP53）、低氧誘導(dǎo)因子-1A（HIF-1A）、原癌基因（MYC）5個核心靶點。GO和KEGG富集分析結(jié)果顯示，柴胡皂苷d可能通過磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）信號通路、MAPK信號通路、卡波西肉瘤相關(guān)皰疹病毒感染等通路起到治療鼻咽癌的作用。分子對接結(jié)果顯示柴胡皂苷d與核心靶點對接結(jié)合能均小于−7.7 kcal/mol。結(jié)論 柴胡皂苷d可通過多靶點和多通路的途徑發(fā)揮治療鼻咽癌的作用。

Objective To explore the mechanism of saikosaponin d in treatment of nasopharyngeal carcinoma through network pharmacology and molecular docking.Method The potential targets of the drug bupleuronate d were predicted through the SwissTartgetPrediction, Stitch, and GeneCards databases, and the nasopharyngeal carcinoma targets were obtained by searching the DrugBank, GeneCards, TTD, Omim, and Pharmgkb databases. The intersection target of saikosaponin d and nasopharyngeal carcinoma was obtained using R 4.3.1 software. STRING database were used to construct the PPI network of intersection targets. Cytoscape software was used to further screen the core targets from the targets screened in the STRING database. The intersection target of saikosaponin d and nasopharyngeal carcinoma was analyzed for GO enrichment and KEGG pathway enrichment using the “ClusterProfiler” package of R4.3.1 software. Mechanism of saikosaponin d in treatment of nasopharyngeal carcinoma was clarified through molecular docking.Result 140 Saikosaponin d targets were predicted, 2 854 nasopharyngeal carcinoma disease targets were screened and deduplicated, and finally 74 intersecting targets were obtained, including 5 core targets including STAT3, MAPK1, TP53, HIF1A, MYC, etc. The GO and KEGG enrichment analysis results showed that saikosaponin d may play a therapeutic role in nasopharyngeal carcinoma through pathways such as PI3K/Akt signaling pathway, MAPK signaling pathway, and Kaposi's sarcoma associated herpesvirus infection. The molecular docking results showed that the binding energy between saikosaponin d and the core target was less than −7.7 kcal/mol.Conclusion Saikosaponin d can exert therapeutic effects on nasopharyngeal carcinoma through multi-target and multi pathway pathways.

R285

廣東醫(yī)科大學(xué)青年科研培育基金（GDMUQ2022013）