Selected by bioinformatics and molecular docking analysis, Dhea and 2–14,15-Eg are effective against cholangiocarcinoma

xlomafota13 shared this article with you from Inoreader Selected by bioinformatics and molecular docking analysis, Dhea and 2–14,15-Eg are effective against cholangiocarcinoma Via Head and neck cancers by Lei Qin, Jun Kuai, Fang Yang, Lu Yang, Peisheng Sun, Lanfang Zhang, Guangpeng Li Object To identify novel targets for the diagnosis, treatment and prognosis of cholangiocarcinoma, we screen ideal lead compounds and preclinical drug candidates with MYC inhibitory effect from the ZINC database, and verify the therapeutic effect of Dhea and 2–14,15-Eg on cholangiocarcinoma. Methods The gene expression profiles of GSE132305, GSE89749, and GSE45001 were obtained respectively from the Gene Expression Omnibus database. The DEGs were identified by comparing the gene expression profiles of cholangiocarcinoma and normal tissues. GO, KEGG analysis and PPI network analyses were performed. LibDock, ADME and toxicity prediction, molecular docking and molecular dynamics simulations were used to identify potential inhibitors of MYC. Moreover, in vitro, MTT assay, colony-forming assay, the scratch assay and Western blotting were performed to verify the therapeutic effect of Dhea and 2–14,15-Eg. Results PPI network analysis showed that ALB, MYC, APOB, IGF1 and KNG1 were hub genes, of which MYC was mainly studied in this study. A battery of computer-aided virtual techniques showed that Dhea and 2–14,15-Eg have lower rodent carcinogenicity, Ames mutagenicity, developmental toxicity potential, and high tolerance to cytochrome P4502D6, as well as could exist stably in natural circumstances. In vitro assays showed that Dhea and 2–14,15-Eg inhibited cholangiocarcinoma cellular viability, proliferation, and migration inhibiting expression of MYC. Conclusion This study suggested that Dhea and 2–14,15-Eg were novel potential inhibitors of MYC targeting, as well as are a promising drug in dealing with cholangiocarcinoma and have a perspective application. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.