雌、孕激素受体在托瑞米芬逆转MCF7/ADR细胞耐药中的作用  

Role of estrogen receptor/progesterone receptor in toremifene-induced reversal of multidrug resistance in MCF7/ADR cells

作　　者：王红霞[1] 张凤春[1] 唐雷[1] 许琦[1] 徐成瑜[1] 

机构地区：[1]上海交通大学医学院附属仁济医院肿瘤科,上海200127

出　　处：《肿瘤》2007年第7期518-522,共5页Tumor

基　　金：上海高等学校科学技术发展基金项目(编号:02BK15)

摘　　要：目的:研究托瑞米芬(toremifene,TOR)对MCF7/ADR细胞耐药的逆转作用及雌孕激素受体可能在其中发挥的作用。方法:采用SRB法测定TOR的耐药逆转倍数;流式细胞仪测定加入TOR后耐药细胞内Rhodamine123荧光含量表达变化;Western blot检测TOR对P-gp表达的影响;免疫组化测定TOR对细胞雌孕激素受体表达情况的影响。结果:5、10、20mol/L的TOR对MCF7/ADR耐药的逆转倍数分别为1.5、7.0、35.4倍,而对MCF7/S细胞没有显著性作用。加入TOR后,MCF7/ADR细胞内ADR荧光的呈现由核外进入核内,荧光含量显著提高,接近于敏感细胞。MCF7/S细胞中P-gp表达阴性,而MCF/ADR细胞中P-gp表达阳性。5、10、20mol/LTOR对MCF7/ADR细胞中P-gp表达未产生显著性抑制作用。MCF7/S细胞的雌激素受体表达阳性,孕激素受体表达弱阳性。MCF7/ADR细胞的雌、孕激素受体表达均阴性。10mol/LTOR对MCF7/S、MCF7/ADR细胞的雌、孕激素受体表达没有影响。结论:TOR可显著逆转MCF7/ADR细胞对ADR的耐药性。其逆转作用与雌、孕激素受体表达情况无明显关系,可能是通过抑制P-gp药泵功能来实现的。Objective： To study the reversing effect of toremifene （TOR） on multidrug resistance （MDR） in drug-resistant （MCF7/ADR） cell lines and its relationship with expression of estrogen receptor/progesterone receptor （ER/PR） in vitro. Methods： SRB method was used to determine the reversal time of toremifene on MDR in MCF7/ADR cells. Flow cytometry was applied to analyze the change in rhodamine 123 fluorescence in MCF7/ADR cells after addition of toremifene. The effect of toremifene on P-glycoprotein （P-gp） expression in MCF7/ADR cells was examined by western blot. Immunohistochemistry was applied to analyze the effect of toremifene on expression of ER/PR. Results：TOR （5, 10, and 20 mol/L） increased the in vitro cytotoxicity of doxorubicin in drugresistant breast cancer cells （reversing times： 1.5-fold, 7.0-fold and 35.4-fold, respectively） but had no significant effect on drug-sensitive MCF7/S cells. Toremifene significantly enhanced intracellular accumulation of rhodamine 123 in drug-resistant MCF7/ADR cells. The intracellular fluorescence was close to sensitive MCF7/S cells. P-gp had negative expression in MCF7/S cells and was positively expressed in MCF7/ADR cells. TOR （5, 10, and 20 mol/L） had no significantly inhibitory effect on the expression of P-gp in MCF7/ ADR cells. The expression of ER was positive and the expression of PR was weak in MCF7/S cells. Both ER and PR were negatively expressed in MCF7/ADR cells. Conclusion：TOR significantly reverses the MDR in MCF7/ADR cells, which is independent of the expression of ER/PR, The possible mechanism may be due to suppression of P-gp expression in MCF7/ADR cells.

关 键 词：抗药性 多药 受体 雌激素 受体 孕激素 托瑞米芬 

分 类 号：R737.9[医药卫生—肿瘤] R73-361[医药卫生—临床医学]