奥美拉唑增强多柔比星对肺腺癌A549细胞毒性作用的实验研究  

Enhanced Cytotoxicity of Doxorubicin against Lung Adenocarcinoma Cell Line A549 in vitro by Omeprazole

作　　者：郭喜喜[1] 汪文东[1] 王家顺[1] 丁静民[1] 张俊[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院胸外科,武汉430022

出　　处：《华中科技大学学报（医学版）》2012年第5期593-596,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

摘　　要：目的探讨囊泡型质子泵(V-ATPase)非特异性抑制剂奥美拉唑(OME)增强多柔比星(ADM)对人肺腺癌细胞株A549的毒性作用及其可能机制。方法 OME(终浓度为0、2.0、4.0、8.0、16.0μg/mL)处理A549细胞48h后,锥虫蓝法测定OME对A549的细胞毒性。OME预处理0、24h后,MTT法测定ADM对A549细胞的半数抑制浓度(IC50)。以非细胞毒性的OME 4μg/mL预处理,流式细胞术测定不同时间A549细胞内ADM的浓度。RT-PCR法测OME预处理后A549细胞内多药耐药基因(MDR1)转录量。结果不同浓度OME预处理的A549细胞锥虫蓝染色均未见蓝染细胞。与对照组比较,OME预处理后,ADM对A549细胞的IC50值明显下降(P<0.05);A549细胞摄入ADM量增加,排出量下降;A549细胞内MDR1基因转录明显下降。结论 OME对A549细胞无毒性作用,但能增强ADM对A549细胞的毒性,其可能机制为OME抑制MDR1基因的转录。Objective To investigate whether omeprazole（OME）,a nonspecific inhibitor of V-ATPase,can enhance the cytotoxicity of doxorubicin against human lung adenocarcinoma cell line A549 and the possible mechanisms.Methods A549 cells were incubated with OME（final concentration of 0,2.0,4.0,8.0 and 16.0 μg/mL）for 48 h,and Trypan blue assay was used to detect the cytotoxicity of OME against A549 cells.A549 cells were pretreated with OME for 0 or 24 h,and the half concentration（IC50）of doxorubicin against A549 cells were measured by using MTT assay.A549 cells were pretreated with OME at non-toxic concentration 4 μg/mL,and the intracellular amount of ADM was detected by using flow cytometry（FCM）at different time points.The transcription of MDR1 was measured by using semi-quantitative reverse transcription polymerase chain reaction（RT-PCR）after pretreatment of A549 cells with OME.Results After pretreatment with different concentrations of OME,no blue cells were observed by using Trypan blue assay.As compared with control group,IC50 of ADM against A549 cells was reduced after pretreatment with OME（P0.05）;The ADM intake by A549 cells was significantly increased and ADM output by A549 cells significantly decreased;the mRNA expression of MDR1 decreased in A549 cells.Conclusion OME had no cytotoxicity against A549 cells,but it can enhance the cytotoxicity of doxorubicin in vitro,probably by inbibiting the mRNA expression of MDR1.

关 键 词：肺肿瘤 耐药 奥美拉唑 V-ATPASE 多柔比星 A549细胞 

分 类 号：R734.2[医药卫生—肿瘤]