乳腺癌CYP1B1的表达对紫杉醇耐药性的影响  

The Role of CYP1B1 in Paclitaxel Resistance in Breast Cancer

作　　者：任杰[1] 李迺昶 李晓蕾[1] 李会强[1] 傅正[1] 朱志峰[1] 

机构地区：[1]天津医科大学免疫教研室,天津市300070 [2]天津医科大学生化教研室,天津市300070

出　　处：《中国肿瘤临床》2012年第23期1904-1908,共5页Chinese Journal of Clinical Oncology

基　　金：天津市滨海新区创新基金(编号:2011-BK1200117)资助~~

摘　　要：目的:探讨乳腺癌细胞CYP1B1表达与紫杉醇耐药产生的相关性。方法:以乳腺癌细胞系MCF-7为研究对象,经TCDD诱导MCF-7表达CYP1B1,观察CYP1B1表达后对紫杉醇药物的细胞毒效应的影响。将紫杉醇联合CYP1B1的拮抗剂ANF使用,观察ANF是否可逆转CYP1B1对紫杉醇的耐药作用。采用RT-PCR测定诱导后CYP1B1 mRNA水平,采用细胞免疫化学染色和蛋白印迹技术测定诱导后CYP1B1蛋白水平,MTS比色法测定紫杉醇对细胞增殖的抑制强度。结果:TCDD可诱导MCF-7细胞表达CYP1B1,其mRNA和蛋白表达水平与TCDD浓度具有明显的剂量依赖性(P<0.05);而单独紫杉醇不能诱导MCF-7细胞表达CYP1B1。当MCF-7细胞经TCDD诱导表达CYP1B1后,紫杉醇浓度在0.01～0.1μg/mL时,紫杉醇对MCF-7细胞的抑制率与对照组相比明显下降(P<0.05)。使用CYP1B1的特异性拮抗剂ANF后,MCF-7细胞对紫杉醇的敏感性升高,细胞抑制率与对照组比较无显著性差异(P>0.05)。结论:CYP1B1表达后可导致细胞产生对紫杉醇耐药。Objective： To study the relevance between CYP1B1 expression and paclitaxel resistance in human breast cancer cell line. Methods： Using human breast cancer cell line MCF-7 as model to observe the effect of CYP1B1 expression which induced by 2,3,7, 8-Tetrachlorodibenzo-p-dioxin （TCDD） on paclitaxel resistance. To observe if pacilitaxel resistance of MCF-7 is specifically induced by CYP1B1 expression. We treated MCF-7 with CYP1B1 specific inhibitorct-naphthoflavone combined with paclitaxel. RT-PCR was used to detect the CYP 1B 1 mRNA expression; CYP 1B 1 protein expression was detected by cell immunochemical staining and Western blotting. The cytotoxicity ofpaclitaxel was assayed by MTS method. Results： TCDD can induce human breast cancer cell line MCF-7 stably express CYP1B1, CYP1B1 mRNA and protein expression have dose dependency with the concentration of TCDD（P〈0.05）;Paclitaxel can not induce MCF-7 cell line express CYP 1B 1 .Treated MCF-7 cell line with paclitaxel at different concentration （0.01-0.1 μg/ml）, the inhibitory rate of paclitaxel on CYP1B1 expression group was reduced significantly（P〈0.05）,compared with control group. This paclitaxel resistance can be reversed by 10 μmol/L ANF. Conclusion： In human breast cell line MCF-7, CYP 1B 1 expression which was induced by TCDD can increase tumor cells survival and lead to paclitaxel resistance.

关 键 词：人乳腺癌细胞MCF-7 2 3 7 8-四氯二苯并二恶英 细胞色素P4501B1 α-奈黄酮 紫杉醇耐药 

分 类 号：R737.9[医药卫生—肿瘤]