尼卡地平对胰腺癌Patu8988株培美曲塞耐药的逆转作用  

Nicardipine reverses the resistance of human pancreatic carcinoma Patu8988 cell line to pemetrexed

作　　者：杨军[1,2] 石欣[1,2] 严伟[1,2] 林士波[1,2] 顾海涛[1,2] 钱程佳[1,2] 

机构地区：[1]东南大学临床医学院 [2]东南大学中大医院普外科,江苏省南京市210009

出　　处：《世界华人消化杂志》2010年第2期132-136,共5页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.30772541;新世纪优秀人才支持计划基金资助项目;NCET-06-0469~~

摘　　要：目的:探讨ABCG2拮抗剂-尼卡地平在体外安全剂量下能否逆转耐药,为临床应用提供实验基础.方法:采用噻唑蓝法(MTT)测定尼卡地平对Patu8988亲本和耐药细胞的安全使用浓度,测定单用培美曲塞和联合安全剂量的尼卡地平分别对两株细胞的IC50变化;分别采用DAPI核染色和细胞流式分析在耐药细胞中单用培美曲塞组和联合尼卡地平组凋亡差异.结果:MTT结果显示尼卡地平在浓度<4.85μmol/L(2.5mg/L)时对细胞基本无不良反应.单用培美曲塞和联合安全剂量的尼卡地平对Patu8988亲本株细胞IC50无明显差异,而对耐药株细胞IC50有差异(P<0.05).流式细胞分析在耐药细胞中联合尼卡地平组凋亡比例高于单用培美曲塞组(32.27%±2.8%vs50.5%±4.2%,P<0.05).结论:安全剂量下尼卡地平能提高胰腺癌Patu8988耐药细胞株对培美曲塞的敏感性,而对其亲本株无作用.AIM：To investigate whether safe doses of nicardipine,an antagonist of ATP-binding cassette subfamily G member 2 （ABCG2）,can reverse the resistance of human pancreatic carcinoma Patu8988 cell line to pemetrexed.METHODS：The maximal safe dose of nicardipine for pemetrexed-resistant Patu8988 strain and its parent strain was determined by methyl thiazoly tetrazolium （MTT） assay.The half maximal inhibitory concentrations （IC 50） of pemetrexed alone and in combination with nicardipine for the growth of the two cell strains were measured also by MTT assay.The apoptosis rates of the two cell strains were examined using DAPI nuclear staining and flow cytometry.RESULTS：MTT analysis showed that the maximal safe dose of nicardipine for Patu8988 strains was 4.85 μmol/L （2.5 mg/L）.Although there was no significant difference in the IC 50 value in parental Patu8988 cell strain between pemetrexed alone and pemetrexed in combination with safe doses of nicardipine,a significant difference was noted in the IC 50 value in drug-resistant Patu8988 strain （P 〈0.05）.Flow cytometry analysis showed that the apoptosis rate of drugresistant cells treated with pemetrexed in combination with nicardipine was higher than that of cells treated with pemetrexed alone （32.27% ± 2.8% vs 50.5% ± 4.2%,P 〈0.05）.CONCLUSION：Nicardipine at safe doses can increase the sensitivity of drug-resistant Patu8988 cell strain to pemetrexed,but has no significant effect in parental Patu8988 strain.

关 键 词：胰腺癌 培美曲塞 耐药 尼卡地平 

分 类 号：R735.9[医药卫生—肿瘤]