Ad-p53逆转乳腺癌细胞株多药耐药性及其对P-gp、TOPOⅡ和GST-π表达的影响  

The effects of Ad-p53 on the reversal of multidrug resistance in human breast cancer cell line and its impacts on the expressions of P-gp,TOPOⅡ and GST-π

作　　者：常志坤[1] 戚晓东[1] 赵广章[1] 杨之斌[1] 

机构地区：[1]首都医科大学附属北京同仁医院肿瘤中心,北京100730

出　　处：《中国癌症杂志》2007年第12期939-941,共3页China Oncology

摘　　要：背景与目的:肿瘤细胞对抗癌药物产生耐受性是化疗失败的主要原因,突变型p53基因与肿瘤多药耐药密切相关。本研究旨在探讨腺病毒介导的p53基因(Ad-p53)对人乳腺癌多柔比星(阿霉素)耐药细胞株MCF-7/Adr多药耐药的逆转作用及其对耐药相关蛋白P-gp、TOPOⅡ和GST-π表达的影响。方法:以人乳腺癌MCF-7细胞及其多柔比星耐药株MCF-7/Adr为实验对象,cck-8法观察Ad-p53对多药耐药的逆转作用,Western blot检测P-gp、TOPOⅡ和GST-π蛋白表达的变化。结果:50MOI Ad-p53能使多柔比星对MCF-7/Adr细胞IC50由(4.54±0.91)μg/ml降到(0.26±0.11)μg/ml,逆转耐药倍数为18.1倍(P<0.001);P-gp、GST-π蛋白表达量下降,TOPOⅡ未见明显变化。结论:Ad-p53能够逆转MCF-7/Adr多药耐药,下调P-gp和GST-π表达。Background and purpose： Multidrug resistance（MDR） is the main obstacle of chemotherapy in the treatment of cancer, and it has been reported that the muted p53 gene is related to MDR. In this study, we explored whether adenovirus mediated p53 gene （Ad-p53） could reverse MDR of human breast caneer and its impacts on the expressions of P-gp, TOPO Ⅱ and GST-π. Methods： In this study, adriamycin-resistant human breast carcinoma cells（MCF-7/Adr） and its parental c.ells（MCF-7） were used to determine the effeet of Ad-p53. Cek-8 assay was adopted to evaluate the cytotoxicity of adriamyein. Western blot were performed to observe Ihe expression of P-glyeoprotein（ P-gp）, Topoismerase Ⅱ （TOPO Ⅱ ） and GST-＇rr. Results： After transteetion with 50 MOI Ad-p53, the 50% inhibitory concentration（ 1C50） of adriamyciu to MCF-7/ Adr eells was decreased from （4.54 ± 0.91）μg/ml to （0.26 ±0. 11 ） μml, and the ehemosensitivily increased 18. 1 times （P 〈 0.001）. Western blot analysis showed that the expressinns of P-gp and GST-π were down-regt, lated, and there was no significant change of TOPO Ⅱ expression. Conclusions： Ad-p53 could reverse muhidrug resistance of MCF-7/Adr cells through the dnwu-regulation of P-gp and GST-π expressions.

关 键 词：乳腺肿瘤 p53基凶 多药耐药 耐药逆转 

分 类 号：R73-36[医药卫生—肿瘤]