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

Zhang,Yuanxin; Ge,Yakun; Ping,Xie; Yu,Ming; Lou,Dawei; Shi,Wei

doi:10.3892/mmr.2018.9129

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

Authors:
- Yuanxin Zhang
- Yakun Ge
- Xie Ping
- Ming Yu
- Dawei Lou
- Wei Shi
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Affiliations: College of Biology and Food Engineering, Jilin Institute of Chemical Technology, Jilin City, Jilin 132022, P.R. China, Jilin Entry‑Exit Inspection and Quarantine Bureau, Changchun, Jilin 130062, P.R. China, School of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin City, Jilin 132022, P.R. China, Key Laboratory for Molecular Enzymology and Engineering of The Ministry of Education, School of Life Science, Jilin University, Changchun, Jilin 130012, P.R. China
Published online on: June 5, 2018 https://doi.org/10.3892/mmr.2018.9129
Pages: 1835-1841

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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‑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.

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