Synergistic apoptotic effects of silibinin in enhancing paclitaxel toxicity in human gastric cancer cell lines

Abstract

Gastric cancer (GC) is the 3rd leading cause of tumor-associated mortality worldwide. The efficacy of paclitaxel, a frequently used GC chemotherapeutic agent, is hindered due to drug resistance, dose-induced toxicity and adverse side effects. Silibinin, an active compound of a widely consumed dietary supplement, milk thistle extract, has recently been demonstrated to have strong antitumor efficacy in a human GC cell model. Thus, to enhance the efficacy of GC treatment, the present study evaluated whether silibinin exerted a synergistic therapeutic effect with paclitaxel. It was observed that the combination of silibinin-paclitaxel was able to trigger cell cycle arrest and apoptosis. The cell cycle arrest assay indicated that silibinin and paclitaxel alone induced a G2/M phase arrest, and the silibinin-paclitaxel combination strongly inhibited G2/M cells from entering the S phase. The apoptosis assay and western blot analysis of poly-ADP-ribose polymerase,pro-caspase3andpro-caspase8demonstratedthat silibinin synergized with paclitaxel in promoting SGC-7901 GC cell apoptosis. Furthermore, upregulation of the ratio of apoptosis regulator Bcl-2/apoptosis regulator BAX and tumor necrosis factor receptor superfamily member 6 (Fas)/Fas ligand indicated that the silibinin-paclitaxel combination activated the death receptor-mediated pathway in SGC-7901 cells. The results of the present study suggested that silibinin enhanced the therapeutic potential of paclitaxel against human GC SGC-7901 cells.