Autophagy inhibition by reversine and its suppressive effects on human hepatocellular carcinoma cells.

INTRODUCTION

Therapy for human hepatocellular carcinoma (HCC) remains a great challenge for physicians and patients worldwide. The anti-tumor effects of reversine have attracted much more concerns.

MATERIALS AND METHODS

This study evaluated the growth regulatory effects of reversine on HCC cells lines. Meanwhile, the underlying mechanism including autophagy modulation was also identified.

RESULTS

reversine markedly inhibited the proliferation of both HCC cells and induced cell apoptosis and multinuclear in a dose-dependent manner. In addition, the decreased ratio of LC3II/LC3I as well as elevated p62 expression were observed under reversine treatment, indicating the autophagy inhibition by reversine in HepG2 cell line. Moreover, modulation of autophagy with rapamycin and chloroquine significantly attenuated and enhanced the cytostatic effects of reversine, respectively.

CONCLUSIONS

reversine could reduce the cell viability of HCC cells via inducing cell apoptosis and polyploidy. In addition, cell autophagy was involved and might play a protective role in HCC cells, the joint use of autophagy inhibitor enhanced reversine-mediating antitumor effects. Our data offered novel ideas for comprehensive therapeutic regimes on human hepatocellular carcinoma.