膀胱癌雌激素受体表达与他莫昔芬拮抗治疗的研究  

A Study on the Expression of Estrogen Receptor and the Effect of Tamoxifen Treatment in Bladder Cancer

作　　者：朱斌[1] 杨罗艳[1] 赵晓昆[1] 

机构地区：[1]中南大学湘雅二医院泌尿外科,长沙410011

出　　处：《癌变．畸变．突变》2009年第1期59-61,64,共4页Carcinogenesis,Teratogenesis & Mutagenesis

摘　　要：背景与目的:探讨他莫昔芬(TAM)联合阿霉素(ADM)对膀胱癌BIU-87细胞株生长的抑制作用。材料与方法:采用免疫组织化学法检测雌激素受体的表达;应用MTT法测定不同浓度的TAM(1、5、10μmol/L)及ADM(0.1、1、10μmol/L),单独和联合作用对BIU-87细胞的生长抑制率,观察TAM的增敏作用;采用原位杂交法检测各实验组bcl-2mRNA的水平。结果:膀胱癌BIU-87细胞表达雌激素受体;TAM单独作用在低浓度时(1μmol/L)对BIU-87生长无抑制作用;TAM联合ADM作用时,对BIU-87细胞生长的抑制率增加,其中TAM10μmol/L组增加显著(P<0.05),显示TAM能提高ADM的敏感性,起到化疗的增敏作用;随着TAM浓度的增加和时间的延长,BIU-87细胞bcl-2mRNA的表达下调。结论:他莫昔芬能增加膀胱癌细胞株BIU-87对化疗药物ADM的敏感性,并抑制细胞增殖;其增敏的作用机制可能与bcl-2的表达下调有关。BACKGROUND AND AIM： In this study we tried to evaluate the possible effects on chemosensitization of bladder cancer cell line BIU-87. MATERIALS AND METHODS： The expression of estrogen receptor（ER） was evaluated by immunohistochemical S-P methed. In vitro chemosensitivity tests were done with bladder cancer cell line BIU-87 and Doxorubicin（0.1, 1, 10 μmol/L） in the presence or absence of graded concentrations of Tamoxifen（1, 5, 10 μmol/L） . The growth and the sensitivity to Tamoxifen of cells were investigated by MTT assay. The level of bcl-2 gene mRNA expression was determined by in situ hybridization. RESULTS： Immunohistochemistry showed positive ER in BIU-87 cells. Tamoxifen stimulated a concentration- dependent and time-dependent decrease in bcl-2 mRNA. Tamoxifen at concentrations of 5 and 10 μmol/ L significandy enhanced the cytotoxicity of the chemotherapeutic agent to the cell lines. Tamoxifen alone caused significant toxic effects to BIU-87 at 10 μmol/ L. Tamoxifen at 5 and 10 μmol/ L down-regulated the secretion of bcl-2 in a concentration-dependent manner. The effect of chemosensitization was evident in cells treated with 1,5 and 10 μmol/L Tamoxifen plus Doxonubicin in which 1.77 to 6.96-fold IC50 reduction was observed. CONCLUSION： Tamoxifen increased the chemosensitivity of Tamoxifen in human bladder cancer BIU-87 cell line in vitro, inhibited cell proliferation and promoted apoptosis.

关 键 词：他莫昔芬 膀胱肿瘤 BCL-2 雌激素受体 

分 类 号：R737.14[医药卫生—肿瘤]