目的 通過網(wǎng)絡(luò)藥理學(xué)及分子對接探究尿石素A治療結(jié)腸癌的主要生物過程和信號通路，闡明其作用機制。方法 通過SwissTargetPrediction、Targets SUP-PRED和Cbligand等數(shù)據(jù)庫預(yù)測尿石素A藥物潛在作用靶點，檢索DisGeNET、OMIM、Gene Cards等數(shù)據(jù)庫獲得結(jié)腸癌相疾病靶點；通過Venn圖獲得相關(guān)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)庫篩選的靶點進行網(wǎng)絡(luò)拓撲分析篩選關(guān)鍵靶點；運用David數(shù)據(jù)庫對交集靶點進行基因本體（GO）和京都基因與基因組百科全書（KEGG）通路分析，最后通過分子對接明確尿石素A治療結(jié)腸癌的作用機制。結(jié)果 預(yù)測得到尿石素A靶點260個，篩選、去重得到結(jié)腸癌疾病靶點3 289個，最后得到交集靶點106個。核心靶點21個，得到蛋白激酶B1（Akt1）、表皮生長因子受體（EGFR）、胱天蛋白酶3（CASP3）、雌激素受體1（ESR1）、環(huán)加氧酶2（PTGS2）等10個核心靶點。GO和KEGG分析表示，尿石素A可能通過癌癥通路、癌癥相關(guān)蛋白聚糖通路等治療結(jié)腸癌的作用。分子對接結(jié)果顯示尿石素A與核心靶點對接結(jié)合能均小于−6.9 kcal/mol。結(jié)論 尿石素A可通過多靶點和多通路的途徑發(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

山東省重點研發(fā)計劃項目(2022TZXD0019);山東省自然科學(xué)基金資助項目(ZR2023QH197);山東省高等學(xué)校“青創(chuàng)科技計劃”團隊項目(2019KJM006);棗莊市產(chǎn)學(xué)研聯(lián)合基金項目(2019LHJJ006)