Shikonin Suppresses Cell Tumorigenesis in Gastric Cancer Associated with the Inhibition of c-Myc and Yap-1

被引：3
作者：
Zhang, Fei [1 ]
Chu, Mingliang [1 ]
Liu, Jiemin [2 ]
Zhao, Qi [3 ]
Zhu, Yanqiu [1 ]
Wu, Xuefang [4 ]
机构：
[1] Guizhou Univ Tradit Chinese Med, First Clin Med Coll, Guiyang 550001, Peoples R China
[2] Guizhou Prov Peoples Hosp, Dept Endoscopy, Guiyang 550002, Peoples R China
[3] Guizhou Univ Tradit Chinese Med, Second Clin Med Coll, Guiyang 550001, Peoples R China
[4] Guizhou Prov Peoples Hosp, Dept Pathol, Guiyang 550002, Peoples R China
来源：
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING | 2024年 / 27卷 / 13期
基金：
中国国家自然科学基金;
关键词：
Network pharmacology; shikonin; gastric cancer; c-Myc; Yap-1; cell tumorigenesis; NETWORK PHARMACOLOGY; DRUG-RESISTANCE; APOPTOSIS; MECHANISMS; EXPRESSION; PREDICTION; TARGETS; DOMAIN;
D O I：
10.2174/0113862073254088231020082912
中图分类号：
Q5 [生物化学];
学科分类号：
071010 ; 081704 ;
摘要：
Aim: The study aimed to study the potential roles and mechanisms of shikonin in gastric cancer by network pharmacology and biological experiments. Methods: The key genes and targets of shikonin in gastric cancer were predicted by network pharmacology and molecular docking study. The effect of shikonin on the proliferation, migration, and invasion of gastric cancer cells was detected by the CCK8 method, and wound healing and transwell assays. The expression levels of c-Myc and Yap-1 were detected via western blotting in gastric cancer cells after shikonin intervention. Results: The results of network pharmacology revealed the key target genes of shikonin on gastric cancer cells to be c-Myc, Yap-1, AKT1, etc. GO and KEGG analysis showed regulation of cell migration, proliferation, adhesion, and other biological processes, including the PI3K-Akt signaling pathway, HIF-1 signaling pathway, necroptosis, and other cancer pathways. Molecular docking showed shikonin to be most closely combined with protooncogenes c-Myc and Yap-1. In vitro experiments showed that the proliferation rate, migration, and invasion ability of the gastric cancer cell group decreased significantly after shikonin intervention for 24h. The expression levels of c-Myc and Yap-1 in gastric cancer cells were found to be significantly decreased after shikonin intervention. Conclusion: This study showed protooncogenes c-Myc and Yap-1 to be the core target genes of shikonin on gastric cancer cells. Shikonin may suppress gastric cancer cells by inhibiting the protooncogenes c-Myc and Yap-1. This suggests that shikonin may be a good candidate for the treatment of gastric cancer.
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收藏
页码：1919 / 1929
页数：11
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