Synergistic apoptotic effects of silibinin in enhancing paclitaxel toxicity in human gastric cancer cell lines.
Mol Med Rep. 2018 Aug ;18(2):1835-1841. Epub 2018 Jun 5. PMID: 29901126
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 recentlybeen 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 ableto 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‑caspase 3 and pro‑caspase 8 demonstrated that 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.