摘要
目的探讨肿瘤细胞内还原型谷胱甘肽(GSH)浓度对肿瘤细胞药物敏感性及在肿瘤细胞耐药机制中的作用。方法以马来酸二乙酯(DEM)处理人乳腺癌耐药细胞株MCF-7/ADM和敏感细胞株MCF-7/S,以消耗细胞内GSH,MTT法检测DEM处理前后两种细胞存活率的变化,并采用荧光分光光度法同步检测其细胞内GSH的消耗程度,分析细胞内GSH浓度的变化与MCF-7细胞对ADM敏感性变化间的相关关系。结果0.1μmol/L DEM使MCF-7/ADM细胞内GSH浓度减少37.4%(P<0.01),使MCF-7/S细胞内GSH浓度减少29.7%(P<0.01);ADM亦使细胞内GSH含量呈ADM浓度依赖性的下降;DEM与ADM合用时,GSH浓度显著下降,其下降程度大于DEM和ADM单独应用之和。随着细胞内GSH数量的减少,无论是MCF-7/ADM细胞,还是MCF-7/S细胞,细胞存活率均下降,即对ADM的敏感性均增强(P<0.01)。结论DEM耗竭细胞内GSH的作用与ADM有协同效应,耗竭细胞内GSH可增强人乳腺癌MCF-7/S细胞对ADM的敏感性,部分逆转MCF-7/ADM细胞对ADM的耐药性。
Objective Glutathione（GSH） maintains an optimum cellular redox potential.Elevated levels of GSH render some types of cancer cells resistant against anti-cancer drugs.The aim of this study was to determine the effect of a thiol-depleting agent,diethylmaleate（DEM）,on the sensitivity of human breast cancer cells to ADM.Methods The ADM-resistant human breast cancer MCF-7/ADM cell lines and ADM-sensitive MCF-7/S cell lines were treated by thiol-depleting agent DEM for 3 h respectively.The changes of sensitivity to ADM were then measured by MTT assay.The intracellular GSH contents were examined by fluorescent-spectrophotometry and the correlation between the changes of sensitivity to ADM and the intracellular GSH content was analyzed.Results Treatment of MCF-7/ADM and MCF7/S cells by 0.1 μmol/L DEM for 3 h decreased 37.4% and 29.7% of the intracellular GSH content respectively（P〈0.01）.ADM also decreased intracellular GSH content in a ADM-concentration-dependent manner.The combined use of DEM and ADM depleted the intracellular GSH content in both cells significantly more than the sum of single use of ADM and DEM alone.The sensitivity of both cells to ADM increased with the decline of intracellular GSH content.Conclusion The depletion effect of DEM on the intracellular GSH could be enhanced by ADM and such depletion may be involved in the changes of the sensitivity of MCF/7 cells to ADM.
出处
《四川大学学报（医学版）》
CAS
CSCD
北大核心
2007年第5期770-774,共5页
Journal of Sichuan University(Medical Sciences)
基金
四川省科技厅基金(04JY029-020-2)资助
