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

Fei Zhang; Mingliang Chu; Jiemin Liu; Qi Zhao; Yanqiu Zhu; Xuefang Wu

doi:10.2174/0113862073254088231020082912

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

Comb Chem High Throughput Screen. 2023 Nov 7. doi: 10.2174/0113862073254088231020082912. Online ahead of print.

Authors

Fei Zhang¹, Mingliang Chu², Jiemin Liu³, Qi Zhao¹, Yanqiu Zhu², Xuefang Wu⁴

Affiliations

¹ The Second Clinical Medical College, Guizhou University of Traditional Chinese Medicine, Guiyang 550001, China.
² The First Clinical Medical College, Guizhou University of Traditional Chinese Medicine, Guiyang 550001, China.
³ Department of Endoscopy, Guizhou Provincial People's Hospital, Guiyang 550002, China.
⁴ Department of Pathology, Guizhou Provincial People's Hospital, Guiyang 550002, China.

PMID: 37957853
DOI: 10.2174/0113862073254088231020082912

Abstract

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.

Keywords: Network pharmacology; Yap-1; c-Myc; experimental research; gastric cancer; shikonin.