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氧化苦参碱与血管生成抑制剂NM-3对人胃癌细胞凋亡调控的协同作用。

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

作者信息

Song Ming-Quan, Zhu Jin-Shui, Chen Jin-Lian, Wang Long, Da Wei, Zhu Li, Zhang Wei-Ping

机构信息

Department of Gastroenterology, The Sixth Affiliated Hospital of Shanghai Jiaotong University, Shanghai 200233, China.

出版信息

World J Gastroenterol. 2007 Mar 28;13(12):1788-93. doi: 10.3748/wjg.v13.i12.1788.

DOI:10.3748/wjg.v13.i12.1788
PMID:17465467
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4149953/
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.

摘要

目的

研究氧化苦参碱(OM)与血管生成抑制剂NM-3协同调节人胃癌细胞系SGC-7901、MKN-45、MKN-74凋亡的作用。

方法

人胃癌细胞系SGC-7901、MKN-45、MKN-74分别在有无NM-3存在的情况下用OM处理。采用MTT法检测抑制率。通过半定量RT-PCR和蛋白质印迹法检测OM和NM-3对SGC-7901细胞中survivin、bcl-2、bax和p53表达的协同作用,并观察它们对裸鼠体内SGC-7901肿瘤异种移植瘤的生长抑制作用。

结果

OM与NM-3联合应用对SGC-7901、MKN-45和MKN-74细胞的生长呈现出时间依赖性的协同抑制作用。用OM、单独的NM-3及其联合处理24小时后,SGC-7901细胞中survivin和bcl-2的mRNA表达下降,p53 mRNA表达增加。与单独使用任一药物相比,OM(4 g/L)与NM-3联合使用显著增加了p53 mRNA的表达,降低了survivin和bcl-2的表达(193%±34%对129%±12%;44%±18%对92%±18%;36±17%对93%±23%,P<0.05)。蛋白质印迹法显示,OM和NM-3对survivin、bcl-2和p53蛋白质翻译的协同作用与其mRNA水平一致。此外,与单独使用任一药物相比,OM/NM-3联合应用对人胃癌异种移植瘤SGC-7901明显表现出抗肿瘤生长作用。

结论

OM与NM-3联合应用对人胃癌细胞在体外具有协同抑制作用,且能在体内抑制人胃癌异种移植瘤SGC-7901的生长。

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