Synergistic anticancer effects of bufalin and sorafenib by regulating apoptosis associated proteins.

Abstract

As one of the most recognized and well-known drugs for hepatocellular carcinoma (HCC), the antitumor effect of sorafenib against HCC remains to be improved. Bufalin has displayed an antitumor effect in HCC; however, whether the enhanced antitumor effect may be generated with their combined treatment remains unclear. Therefore, in the present study, their combined effects on HCC proliferation and apoptosis were investigated. It was revealed that either bufalin or sorafenib suppressed PLC/PRF/5 and SMMC-7721 cell proliferation in a concentration-dependent manner following incubation for 24 h, and the inhibitory effect was augmented with their combined treatment. The synergistic effect peaked in HCC cells treated with 20 nM bufalin and 10 µM sorafenib. In addition, cell cycle and terminal deoxynucleotidyl transferase dUTP nick-end labelling assays revealed that bufalin also enhanced sorafenib-induced apoptosis. Colony formation assay demonstrated that combined treatment significantly suppressed HCC proliferation compared with treatment with either of them alone. Furthermore, B-cell lymphoma 2-associated X protein, caspase 7 and poly-(adenosine diphosphate-ribose) polymerase were upregulated in HCC cells with combined treatment. Taken together, the results of the present study revealed that the treatment of sorafenib combined with bufalin synergistically suppressed HCC proliferation and induced apoptosis. Therefore, bufalin combined with sorafenib may be a favorable treatment strategy for patients with HCC.