Artemether inhibits proliferation, invasion and migration of hepatocellular carcinoma cells via targeting of CYP2J2.

Abstract

Artemether, a natural derivative of artemisinin, serves an antitumor role in numerous types of cancer. However, the role and mechanism of action of artemether in hepatocellular carcinoma (HCC) has remained elusive. The present study aimed to investigate whether artemether is able to inhibit the proliferation, invasion and migration of HCC cells by targeting cytochrome P450 family 2 subfamily J member 2 (CYP2J2). Cell Counting Kit-8 (CCK-8) and colony-formation assays were used to examine cell viability. Wound-healing and Transwell assays were used to evaluate the cell invasion and migration ability. The expression levels of the epithelial-mesenchymal transition-related proteins E-cadherin, N-cadherin and vimentin were detected via western blot analysis. To determine the mechanism of the inhibitory effect of artemether on HCC, CYP2J2 was overexpressed and its expression in cells treated with artemether was confirmed using reverse transcription-quantitative PCR and western blot analysis. The effects of artemether on the viability, proliferation and migration of HCC cells overexpressing CYP2J2 were detected using CCK-8, colony-formation, wound-healing and Transwell assays, respectively. Artemether was demonstrated to exert a significant inhibitory effect on the proliferation, invasion and migration of HCC cells. Furthermore, artemether also inhibited CYP2J2 expression in Hep3B2.1-7 cells and CYP2J2 overexpression reversed the inhibitory effect of artemether on the proliferation, invasion and migration of HCC cells. Overall, these results indicated that artemether may inhibit HCC cell proliferation, invasion and migration via targeting CYP2J2. These findings may provide potential targets for future HCC therapeutics.