Sanguinarine promotes apoptosis of hepatocellular carcinoma cells via regulating the miR-497-5p/CDK4 axis.

Objective: To determine the effect of sanguinarine on the biological behavior of hepatocellular carcinoma (HCC) cells via regulating the miR-497-5p/cyclin-dependent kinase 4 (CDK4) axis.

Methods: Swiss Target Prediction was used for target prediction of sanguinarine. The targets were analyzed with KEGG enrichment analysis, and CDK4 was included in this study. Target prediction website, Diana tools enrichment analysis, and dual-luciferase reporter assay were adopted to identify the target miRNAs for CDK4. We measured expression levels of CDK4 and miR-497-5p in cancerous tissues, normal liver L02 cells, HepG2 HCC cells and sanguinarine-treated HepG2 cells. The expression of CDK4/miR-497-5p in HCC cells was intervened by treating HCC cells with sanguinarine. Cell proliferation, invasion and apoptosis were measured with CCK8, Transwell and flow cytometry, respectively.

Results: CDK4 was shown to be a target for sanguinarine. Compared with L02 cells, CDK4 expression in HCC cells was significantly increased, but sanguinarine inhibited the CDK4 expression in HCC cells. The proliferation and invasion of HCC cells were inhibited, and the apoptosis was promoted by sanguinarine, but these effects were reversed by CDK4 overexpression (both P<0.05). miR-497-5p was confirmed to be a target miRNA for CDK4, and its expression was decreased in HCC cells but could be promoted by sanguinarine. The effect of miR-497-5p knockdown on HCC cells was partially reversed by si-CDK4.

Conclusion: Sanguinarine inhibits the proliferation and invasion of HCC cells, and induces the apoptosis of HCC cells by regulating the expression of miR-497-5p/CDK4.