目的 通過(guò)網(wǎng)絡(luò)藥理學(xué)及分子對(duì)接探究尿石素A治療結(jié)腸癌的主要生物過(guò)程和信號(hào)通路，闡明其作用機(jī)制。方法 通過(guò)SwissTargetPrediction、Targets SUP-PRED和Cbligand等數(shù)據(jù)庫(kù)預(yù)測(cè)尿石素A藥物潛在作用靶點(diǎn)，檢索DisGeNET、OMIM、Gene Cards等數(shù)據(jù)庫(kù)獲得結(jié)腸癌相疾病靶點(diǎn)；通過(guò)Venn圖獲得相關(guān)交集靶點(diǎn)。運(yùn)用STRING數(shù)據(jù)庫(kù)構(gòu)建交集靶點(diǎn)的蛋白相互作用（PPI）網(wǎng)絡(luò)；使用Cytoscape軟件對(duì)STRING數(shù)據(jù)庫(kù)篩選的靶點(diǎn)進(jìn)行網(wǎng)絡(luò)拓?fù)浞治龊Y選關(guān)鍵靶點(diǎn)；運(yùn)用David數(shù)據(jù)庫(kù)對(duì)交集靶點(diǎn)進(jìn)行基因本體（GO）和京都基因與基因組百科全書(shū)（KEGG）通路分析，最后通過(guò)分子對(duì)接明確尿石素A治療結(jié)腸癌的作用機(jī)制。結(jié)果 預(yù)測(cè)得到尿石素A靶點(diǎn)260個(gè)，篩選、去重得到結(jié)腸癌疾病靶點(diǎn)3 289個(gè)，最后得到交集靶點(diǎn)106個(gè)。核心靶點(diǎn)21個(gè)，得到蛋白激酶B1（Akt1）、表皮生長(zhǎng)因子受體（EGFR）、胱天蛋白酶3（CASP3）、雌激素受體1（ESR1）、環(huán)加氧酶2（PTGS2）等10個(gè)核心靶點(diǎn)。GO和KEGG分析表示，尿石素A可能通過(guò)癌癥通路、癌癥相關(guān)蛋白聚糖通路等治療結(jié)腸癌的作用。分子對(duì)接結(jié)果顯示尿石素A與核心靶點(diǎn)對(duì)接結(jié)合能均小于−6.9 kcal/mol。結(jié)論 尿石素A可通過(guò)多靶點(diǎn)和多通路的途徑發(fā)揮治療結(jié)腸癌的功效。

Objective To investigate the main biological processes and signaling pathways of mechanism urolithin A in treatment of colon cancer through network pharmacology and molecular docking, and elucidate its action. Methods To predict the potential targets of urolithin A by SwissTargetPrediction, Targets SUP-PRED, and Cbligand database. To obtain the target information of colon cancer through DisGeNET, OMIM, Gene Cards. The intersection targets of urolithin A and colon cancer were obtained by Venn diagram. PPI network of intersection targets was constructed by STRING database. Perform network topology analysis on the target genes selected from the STRING database using the Cytoscape software to identify key target genes. David database was used to analyze the GO and KEGG pathway analysis of intersection targets. Finally, mechanism of action of urolithin A and key targets was further clarified by molecular docking. Results A total of 260 urolithin A targets were predicted, 3 289 colon cancer disease targets were obtained by screening and deduplication, and 108 intersection targets were finally obtained. Ten core targets were obtained, including protein kinase B1 (Akt1), epidermal growth factor receptor (EGFR), Caspase 3 (CASP3), estrogen receptor 1 (ESR1), and cycloxygenase 2 (PTGS2). GO and KEGG enrichment analysis mainly urolithin A may play a role in treatment of colon cancer through pathways in cancer, proteoglycans in cancer. Results of molecular docking showed that the binding energy of urolithin A to key targets was less than −6.9 kcal/mol. Conclusion Urolithin A may regulate more pathways and more targets to play a role in treatment of colon cancer.

R965

山東省重點(diǎn)研發(fā)計(jì)劃項(xiàng)目(2022TZXD0019);山東省自然科學(xué)基金資助項(xiàng)目(ZR2023QH197);山東省高等學(xué)?！扒鄤?chuàng)科技計(jì)劃”團(tuán)隊(duì)項(xiàng)目(2019KJM006);棗莊市產(chǎn)學(xué)研聯(lián)合基金項(xiàng)目(2019LHJJ006)