脱嘌呤/脱嘧啶核酸内切酶/氧化还原因子-1基因与乳腺癌细胞对吉西他滨耐药的相关性研究  

Relationship on chemoresistance between the apurinic/apyrimidinic endonuclease /redox factor-1 in breast cancer with induction of gemcitabine

作　　者：郑敏[1] 曹永晋[2] 蔡伟华[2] 

机构地区：[1]福建医科大学附属第一医院化疗科,福州350004 [2]福建医科大学附属第一医院甲状腺乳腺科,福州350004

出　　处：《中国临床药理学杂志》2015年第10期858-860,共3页The Chinese Journal of Clinical Pharmacology

基　　金：福建省卫生厅青年科研基金资助项目(2012-2-45)

摘　　要：目的研究人乳腺癌MCF-7细胞株经吉西他滨处理后APE/Ref-1mRNA和蛋白表达的变化。方法以50 nmol·L-1吉西他滨处理乳腺癌MCF-7细胞,在处理后0,3,7,10,13和16天,测定细胞凋亡比例、存活细胞APE/Ref-1基因mRNA及蛋白表达情况。结果吉西他滨50 nmol·L-1干预后第0,3,7,10,13,16天,细胞APE/Ref-1 mRNA及蛋白表达水平均逐渐增加,与干预天数呈正相关,并与凋亡细胞比例的变化趋势一致。APE/Ref-1表达水平从第10天起明显增加,第16天达到最高(P<0.05)。并且干预至第10,13,16天后,细胞中的APE/Ref-1 mRNA和蛋白表达水平与药物干预前细胞相比有明显差别(P<0.05)结论 APE/Ref-1在乳腺癌化疗时表达明显增强,可能与化疗耐药性的产生有关。Objective To investigate the changes of apurinic/apyrimidi-nic endonuclease/redox factor -1 （ APE/Ref -1 ） expression in human breast cancer cell line MCF -7 after induction of gemcitabine and to study the effects of gemcitabine on chemoresistance in breast cancer . Methods After human breast cancer cell line MCF -7 was incubated with 50 nmol· L-1 concentration of gemcitabine for 0,3,7,10,13 and 16 days, the apoptosis ratio was determinated by flow cytometry .And the mRNA and protein levels of APE/Ref -1 of survival cells were deter-mined by reverse transcription -polymerase chain reaction （ RT-PCR） and Western blot , respectively.Results After human breast cancer cell line MCF-7 was incubated with 50 nmol· L -1 gemcitabine for 0,3,7, 10,13 and 16 days,the expression of APE/Ref-1 in human breast can-cer cell line MCF-7 was elevated significantly both at mRNA and pro-tein levels ,and were positively correlated with incubation time , which is consistent with the proportion of apototic cells .And the expression of APE/Ref-1 was increasing significantly from tenthdays , reaching the highest in sixteenth days .And when the drug resistant cells was com-pared with the non -drug resistant cells , which were both incubated with 50 nmol· L-1 gemcitabine for 10,13 and 16 days.The expression of mRNA and protein of APE/Ref-1 in drug resistant cells have statistical＆amp;nbsp;significance （ P〈0.05 ）.Conclusion The obvious up -regulated expression of APE/Ref-1 may be an adaptive re-sponse contributing to the overall chemoresistance in breast cancer .

关 键 词：吉西他滨 脱嘌呤/脱嘧啶核酸内切酶/氧化还原因子-1 乳腺癌 化疗耐药性 耐药 

分 类 号：R979.1[医药卫生—药品] R969.3[医药卫生—药学]