Gastric Cancer
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Mar 28, 2007; 13(12): 1788-1793
Published online Mar 28, 2007. doi: 10.3748/wjg.v13.i12.1788
Synergistic effect of oxymatrine and angiogenesis inhibitor NM-3 on modulating apoptosis in human gastric cancer cells
Ming-Quan Song, Jin-Shui Zhu, Jin-Lian Chen, Long Wang, Wei Da, Li Zhu, Wei-Ping Zhang
Ming-Quan Song, Jin-Shui Zhu, Jin-Lian Chen, Long Wang, Wei Da, Li Zhu, Wei-Ping Zhang, Department of Gastroenterology, The Sixth Affiliated Hospital of Shanghai Jiaotong University, Shanghai 200233, China
Author contributions: All authors contributed equally to the work.
Supported by Natural Science Foundation of Shanghai, No. 02ZB14072
Correspondence to: Professor Jin-Shui Zhu, Department of Gastroenterology, The Sixth Affiliated Hospital of Shanghai Jiaotong University, Shanghai 200233, China. zhujs1803@hotmail.com
Telephone: +86-21-64369181 Fax: +86-21-64837019
Received: November 3, 2006
Revised: December 3, 2006
Accepted: February 26, 2007
Published online: March 28, 2007
Abstract

AIM: To investigate the synergistic effect of oxymatrine (OM) and angiogenesis inhibitor NM-3 on modulating apoptosis in human gastric cancer cell lines SGC-7901, MKN-45, MKN-74.

METHODS: Human gastric cancer lines SGC-7901, MKN-45, MKN-74 were treated with OM in the absence and presence of NM-3. The inhibitory rates were detected by MTT assay. Synergistic effect of OM and NM-3 on the growth of survivin, bcl-2, bax and p53 in SGC-7901 cells were examined by semiquantitative RT-PCR and Western blotting, and their growth inhibitory effects were also observed on SGC-7901 tumor xenograft in nude mice.

RESULTS: OM combined with NM-3 exhibited a synergistic inhibitory effect on the growth of SGC-7901, MKN-45 and MKN-74 cells in a time-dependent manner. Twenty-four hours after treatment with OM, NM-3 alone and their combination, mRNA expression of survivin and bcl-2 in SGC-7901 cells decreased, p53 mRNA expression increased. OM (4 g/L) combined with NM-3 significantly increased the expression of p53 mRNA and decreased the expression of survivin and bcl-2 compared with either agent alone (193% ± 34% vs 129% ± 12%; 44% ± 18% vs 92% ± 18%; 36 ± 17% vs 93% ± 23%, P < 0.05). Western blotting showed that the synergistic effect of OM and NM-3 on protein translation of survivin, bcl-2 and p53 was in accordance with their mRNAs. Furthermore, OM/NM-3 combination obviously exhibited antitumor growth effect in xenografted human gastric cancer cells SGC-7901 compared with either agent alone.

CONCLUSION: OM combined with NM-3 has synergistic inhibitory effects on human gastric cancer cells in vitro and can suppress the growth of xenografted human gastric cancer cells SGC-7901 in vivo.

Keywords: NM-3 compound; Oxymatrine; Gastric cancer; Apoptosis