Mylabris phalerata induces the apoptosis and cell cycle delay in HCC, and potentiates the effect of sorafenib based on the molecular and network pharmacology approach

Abstract

Background In patients with hepatocellular carcinoma (HCC), surgical treatment may be recommended at an early stage. Sorafenib is the only drug approved for the treatment of advanced HCC, but the survival period is only extended by 2-3 months. Also, sorafenib develops resistance. Objective It needs to find the new chemotherapy drugs for HCC. We investigated growth inhibition of cancer cell by Mylabris phalerata (MP) in the human Huh-7 HCC cell line. Methods Huh-7 cells were treated with MP examined by in vitro assay. And we checked whether MP could increase sensitivity to in vivo model. In addition, we employed the NGS analysis to provide transcriptomic insight. Results MP inhibits growth of HCC cell lines by inducing apoptosis and G2/M cell cycle arrest. MP enhanced AMPK activation and reduced mTOR, and increased cyclin B1 levels. MP also inhibited migration and synergistically enhanced sensitivity to sorafenib in the Huh-7 cells. In the RNA-seq analysis, the differentially expressed genes by MP were primarily associated with extracellular matrix, angiogenesis and migration. Conclusions Our results indicate that MP potentially have anti-cancer effects and might be applied for combination therapy with sorafenib for HCC.