人肺腺癌干细胞对顺铂和卡铂的药物敏感度分析  

The drug sensitivity of human lung adenocarcinoma stem cells to cisplatin and carboplatin

作　　者：黄进肃[1] 亓雪莲[2] 张雪艳[1] 李焱[2] 韩宝惠[1] 耿沁[2] 周瑾[2] 徐惠莉[2] 董强刚[2] 

机构地区：[1]上海交通大学附属胸科医院肺内科,上海200030 [2]上海交通大学肿瘤研究所肿瘤干细胞实验室,上海200032

出　　处：《肿瘤》2010年第2期95-99,共5页Tumor

基　　金：国家自然科学基金资助项目(编号:30872952);上海市科学技术委员会科研计划项目(编号:0852nm05800);上海市科学技术委员会科技发展基金资助项目(编号:09411961700)

摘　　要：目的:分析人肺腺癌干细胞(lung adenocarcinoma stem cell,LASC)对顺铂(cisplatin,DDP)和卡铂(carboplatin,CBP)的药物敏感度。方法:人肺腺癌细胞SPC-A1、AG及CPA-Y2经DDP和CBP作用后,应用CCK-8(cell countingkit-8)比色法检测细胞存活率,应用免疫荧光检测法测定药物生存细胞(drug surviving cell,DSC)的表型特征。通过磁性细胞分选技术分离肺腺癌干细胞,应用绿色荧光蛋白(green fluorescent protein,GFP)示踪技术检测DSC中的肿瘤干细胞,分析DSC对DDP和CBP的药物敏感度。结果:LASC具有细支气管肺泡干细胞(bronchioalveolar stem cell,BASC)表型(OCT4+CCSP+SP-C+)。将此类癌干细胞(CD221+)与肺腺癌分化细胞(CD221-)混合后检测DSC发现,后者具有OCT4+BASC表型。DSC对铂类药物具有显著抗性。结论:肺腺癌干细胞对DDP和CBP具有显著耐药性,可能是化疗后肿瘤复发的根源。Objective：To analyze the drug sensitivity of human lung adenocarcinoma stem cells （LASC） to cisplatin （DDP） and carboplatin （CBP）. Methods：Human lung adenocarcinomaic cells SPC-A1,AG,and CPA-Y2 were treated with DDP and CBP. The cell viability of cells was detected by CCK-8 assay. The phenotypic characteristics of drug surviving cells（DSCs）were determined by immunofluorescence staining. The LASC population was then separated by magnetic-activated cell sorting method. The LASC in DSCs was traced by using green fluorescence protein （GFP）. The drug sensitivity of DSCs to DDP and CBP was analyzed.Results：The LASC exhibited the phenotypes of bronchioalveolar stem cells （BASC,OCT4＋CCSP＋SP-C＋）. After mixture of CD221＋LASC with CD221-lung adenocarcinoma differentiated cells,the DSC population showed OCT4＋BASC phenotypes. These DSCs were significantly resistant to DDP and CBP.Conclusion：LASC has a high resistance to DDP and CBP. This may be the reason for tumor recurrence after chemotherapy.

关 键 词：肺肿瘤 肿瘤干细胞 药物筛选试验 抗肿瘤 顺铂 卡铂 

分 类 号：R734.2[医药卫生—肿瘤]