丁硫氨酸亚砜胺逆转人乳腺癌多药耐药细胞株耐药性的体外研究  

Study on in Vitro Reversing Multidrug Resistance of Human Breast Cancer Cells by Buthionine Sulfoximine

作　　者：娄广媛[1,2] 沈朋[1] 朱赤红[2] 冯建国[2] 凌志强[2] 张沂平[2] 

机构地区：[1]浙江大学医学院附属第一医院肿瘤内科,杭州310003 [2]浙江省肿瘤医院肿瘤内科,杭州310022

出　　处：《中国药学杂志》2012年第17期1370-1373,共4页Chinese Pharmaceutical Journal

基　　金：浙江省医药卫生科技计划项目(2007B025;2008A015;2010KYA032;2010KYA036);浙江省人口计生委基金(2010-29)

摘　　要：目的探讨丁硫氨酸亚砜胺(BSO)对体外培养的人乳腺癌细胞株多药耐药性的影响。方法以谷胱甘肽(GSH)还原酶循环法检测丁硫氨酸亚砜胺处理前后细胞内谷胱甘肽含量的变化;四甲基偶氮唑蓝比色法检测丁硫氨酸亚砜胺预处理对多柔比星(ADM)50%抑制浓度(IC50)的影响并进一步计算耐药倍数和逆转倍数;流式细胞仪检测丁硫氨酸亚砜胺对乳腺癌多耐药细胞株MCF-7/ADM凋亡及细胞周期的影响。结果耐药细胞MCF-7/ADM内谷胱甘肽含量较人乳腺癌MCF-7细胞内谷胱甘肽含量明显增高;丁硫氨酸亚砜胺显著抑制MCF-7/ADM细胞内谷胱甘肽的合成,而对MCF-7细胞内谷胱甘肽合成影响较小;丁硫氨酸亚砜胺在一定浓度范围内能降低多柔比星对MCF-7/ADM细胞的IC50,在50,100,200,400,800μmol.L-1浓度时的耐药的逆转倍数分别为1.25、2.02、8.42、12.65和9.71倍,而对MCF-7细胞的IC50无明显影响;与单纯应用多柔比星组相比,丁硫氨酸亚砜胺及多柔比星联合用药组凋亡细胞比例明显增加,G0/G1期细胞比例增加。结论丁硫氨酸亚砜胺可通过抑制细胞谷胱甘肽的合成,部分逆转乳腺癌耐药细胞的耐药性,这种作用可能是通过诱导细胞凋亡实现的。OBJECTIVE To study the effect of BSO administration on the multidrug resistance （MDR） transformation of human breast cancer cell line in vitro. METHODS The intracellular GSH content was measured by glutathione reduetase recycling assay; the 50% inhibitory concentration （IC50） of ADM was measured by MTT assay, then the multidrug resistance property and multidrug resistance reversal times were determined ; the apoptosis rate and cell cycle of MCF-7/ADM cell both before and after BSO administration were measured by flow cytometry. RESULTS The level of GSH in MCF-7/ADM cells was significantly higher than that in MCF-7 cells ; the BSO treatment exerted significant inhibitory effect on the synthesis of GSH in MCF-7/ADM while slight effect on MCF-7 cell ; The ICs0 of ADM in MCF-7/ADM cells was decreased by BSO of certain doses, the multidrug resistance reversal times by BSO at concentrations of 50, 100,200, 400, and 800 μmol . L 1 were 1.25, 2.02, 8.42, 12. 65, and 9.71 respectively, but BSO had no such effect on MCF-7 cell. The value of apoptosis rate and the cells accumulated in Go/GI phase increased significantly when BSO and ADM were simultaneously used compared with using ADM merely. CONCLUSION BSO can potentially reverse the MDR of MCF-7/ADM cells by inhibition of GSH synthesis in vitro, and the effect may be achieved by inducing apoptotic cell death.

关 键 词：丁硫氨酸亚砜胺 乳腺癌 多药耐药 

分 类 号：R965[医药卫生—药理学]