摘要
目的探讨新的钙阻断剂甲基莲心碱(Nef)对耐长春新碱人胃癌细胞多药耐药性(MDR)的逆转作用及其机制。方法采用MTT比色法,检测药物的细胞毒作用;应用免疫细胞化学SP法及流式细胞术,检测Nef对人胃癌细胞Bcl-2蛋白表达的影响。结果 10μmol/L Nef对SGC7901及SGC7901/VCR无显著细胞毒作用;2.5、5、10μmol/L Nef能使VCR对SGC7901/VCR细胞的IC50从2.32μg/ml依次下降至0.340、0.128、0.053μg/ml,逆转倍数分别为6.8、18.1、43.8。当Nef浓度为10μmol/L时,逆转SGC7901/VCR多药耐药活性较VRP高(P<0.01);SGC7901/VCR细胞中Bcl-2蛋白表达水平较SGC7901细胞高,经Nef处理后,SGC7901/VCR细胞中Bcl-2蛋白表达水平明显下降,表明Nef能下调SGC7901/VCR细胞中Bcl-2蛋白表达水平。结论甲基莲心碱在体外能逆转耐长春新碱人胃癌细胞(SGC7901/VCR)的多药耐药性,其机制可能与下调Bcl-2蛋白表达水平有关。
Objective To study the reversal of multidrug resistance（MDR） and its mechanism by neferine which is a new calcium channel blocker in human gastric carcinoma cell line SGC7901/VCR.Methods The cytotixic effect was tested by MTT assay.The expression of Bcl-2 protein in human gastric carcinoma cells was examined by immunocytochemical and flow cytometry.Results Neferine of the concentration 10 μmol/L was not of significant cytotoxicity to SGC7901 and SGC7901/VCR cells.Neferine of the concentration 2.5,5,10 μmol/L decreased the IC50 value of VCR to SGC7901/VCR cells from 2.32 μg/ml to 0.340,0.128 and 0.053 μg/ml,respectively and with the increase by 6.8-,18.1-and 43.8-fold in the chemosensitivity,respectively.It had more potent reversal action on SGC7901/VCR cells than verapamil at the concentration of 10μmol/L（P〈0.01）.The level of Bcl-2 protein expression was more higher in SGC7901/VCR cells than in SGC7901 cells.After treatment with neferine,the level of Bcl-2 protein expression in SGC7901/VCR cells was significantly down-regulated,which denominated that neferine could decline the level of Bcl-2 protein expression in SGC7901/VCR cells.Conclusion Neferine could reverse multidrug resistance of human gastric carcinoma cells SGC7901/VCR in vitro.Its reversal mechanism might be associated with down-regulation the level of Bcl-2 protein expression in SGC7901/VCR cells
出处
《实用癌症杂志》
2012年第4期334-336,345,共4页
The Practical Journal of Cancer
