化疗药物对人乳腺癌荷瘤裸鼠ER-α表达和甲基化水平的影响  

Effect of chemotherapy drugs on ER-α expression and methylation level in human breast cancer-bearing nude mice

作　　者：孙丽[1] 曹苏生[2] 马晓燕[3] 刘艳华[1] 孙三元[1] SUN Li;CAO Susheng;MA Xiaoyan(Department of Medical Oncology,Xuzhou Central Hospital,Xuzhou 221009,CHINA)

机构地区：[1]徐州市中心医院肿瘤内科,江苏221009 [2]徐州市中心医院乳腺外科,江苏221009 [3]武警湖北总队医院门诊部

出　　处：《江苏医药》2020年第6期593-596,共4页Jiangsu Medical Journal

基　　金：徐州市科技局社会发展项目(KC18191、KC15SX005)。

摘　　要：目的探讨常用化疗药物对人乳腺癌荷瘤裸鼠雌激素受体α(ER-α)表达和甲基化水平的影响。方法 36只裸鼠接种ER阳性表达(ER^+)人乳腺癌细胞株MCF-7,36只裸鼠接种ER阴性表达(ER^-)人乳腺癌细胞株MDA-MB-231。成功建模后,均分别腹腔注射紫杉醇和表柔比星0、1、2、5、10、20 mg/kg,计算肿瘤体积。采用Western blot法检测肿瘤组织中ER-α、DNA甲基转移酶1(DNMT1)和组蛋白去乙酰化酶1(HDAC1)的蛋白表达,定量甲基化特异性PCR检测ER-α甲基化水平。结果紫杉醇和表柔比星腹腔内给药后,肿瘤体积呈剂量依赖性缩小(P<0.05)。ER^+ MCF-7细胞种植瘤中,紫杉醇和表柔比星均可导致ER-α蛋白表达降低(P<0.05),DNMT1和HDAC1蛋白表达增加(P<0.05),ER-α甲基化水平升高(P<0.05)。ER^- MDA-MB-231细胞种植瘤中,紫杉醇和表柔比星引起DNMT1和HDAC1蛋白表达增加(P<0.05);而ER-α甲基化在药物处理前后均保持较高水平(P>0.05)。结论化疗药物紫杉醇和表柔比星可导致ER^+乳腺癌细胞中ER-α表达下降,甲基化水平升高,可能与DNMT1和HDAC1的表达上调有关。Objective To investigate the effect of common chemotherapy drugs on estrogen receptor-α(ER-α) expression and methylation level in human breast cancer-bearing nude mice.Methods A total of 36 nude mice was inoculated with ER-positive expressed(ER^+) human breast cancer cell line MCF-7 and another 36 nude mice were inoculated with ER-negative expressed(ER^-) human breast cancer cell line MDA-MB-231.After model establishment,the mice were intraperitoneally injected with paclitaxel and epirubicin 0,1,2,5,10 and 20 mg/kg,respectively.The tumor volume was calculated.The protein expressions of ER-α,DNA methyltransferase 1(DNMT1) and histone deacetylase 1(HDAC1) in the tumor tissues were detected by Western blot.The methylation level of ER-α was determined by quantitative methylation-specific PCR.Results After treated with paclitaxel and epirubicin,the tumor volume was decreased in a dose-dependent manner(P<0.05).The protein expression of ER-α was decreased(P<0.05),while the protein expressions of DNMT1 and HDAC1 and the methylation level of ER-α were increased after the treatment of paclitaxel and epirubicin in ER^+ MCF-7 xenograft(P<0.05).The protein expressions of DNMT1 and HDAC1 were increased after the treatment of paclitaxel and epirubicin in ER^-MDA-MB-231 xenograft(P<0.05),while ER-α methylation remained at high level before and after drug treatment(P>0.05).Conclusion Chemotherapy drugs could lead to decreased expression of ER-α and increased methylation level of ER-α in breast cancer,which may be related with the up-regulated expressions of DNMT1 and HDAC1.

关 键 词：乳腺癌 雌激素受体 化疗 甲基化 

分 类 号：R737[医药卫生—肿瘤]