Synergistic effect of oxymatrine and angiogenesis inhibitor NM-3 on modulating apoptosis in human gastric cancer cells

Synergistic effect of oxymatrine and angiogenesis inhibitor NM-3 on modulating apoptosis in human gastric cancer cells
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DOI:
10.3748/wjg.v13.i12.1788
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发表时间:
2007-03-28
影响因子:
4.3
通讯作者:
Zhang, Wei-Ping
Zhang, Wei-Ping
中科院分区:
医学2区
文献类型:
--
作者:
Song, Ming-Quan;Zhu, Jin-Shui;Zhang, Wei-Ping

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目的:探讨氧化苦参碱(014)与血管生成抑制剂NM-3协同作用对人胃癌细胞株SGC-7901、MKN-45、MKN-74凋亡的影响。MTT法检测细胞生长抑制率。半定量RTPCR和Western blotting检测OM和NM-3对胃癌细胞株SGC-7901中survivin、bcl-2、bax和p53的协同作用,并观察OM和NM-3对胃癌裸鼠移植瘤的生长抑制作用。OM与NM-3联合应用对胃癌细胞株SGC-7901、MKN-45和MKN-74的生长具有协同抑制作用,且呈时间依赖性。OM、NM-3单独及联合作用24 h后,胃癌细胞株SGC-7901中survivin、bcl-2 mRNA表达降低,p53 mRNA表达升高。OM(4 g/L)与NM-3联合应用可显著增加p53 mRNA的表达,降低survivin和bcl-2的表达(193% +/- 34% vs 129% +/- 12%; 44% +/- 18% vs 92% +/- 18%; 36 +/- 17% vs 93% +/-23%,P < 0.05)。Western blotting结果显示OM和NM-3对survivin、bcl-2和p53蛋白翻译的协同作用与其mRNA表达水平一致。结论:OM与NM-3联合应用对人胃癌细胞株SGC-7901的体外生长具有协同抑制作用,对人胃癌细胞株SGC-7901的体内生长具有抑制作用。(C)2007年,WJG出版社。All rights reserved.
AIM: To investigate the synergistic effect of oxymatrine (014) 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 RTPCR 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.(C) 2007 The WJG Press. All rights reserved.