不同浓度常用化疗药物连续刺激对人肺腺癌细胞株增殖耐药产生的影响  

Effects of repeated treatment with different concentrations of chemotherapy drugs on proliferation and chemo-resistance in human lung cancer cell line

作　　者：迟志宏[1] 李鹏[1] 刘端祺[2] 张积仁[1] 时冉[3] 

机构地区：[1]第一军医大学珠江医院肿瘤科,广州510282 [2]北京军区总医院肿瘤科,北京100700 [3]北京理工大学生命科学与技术学院,北京100081

出　　处：《第二军医大学学报》2004年第7期781-784,共4页Academic Journal of Second Military Medical University

摘　　要：目的 :探讨常用化疗药物连续刺激对肿瘤细胞株增殖及耐药相关蛋白的影响。 方法 :人肺腺癌细胞株 (L TEP- a- 2 )经多柔比星 (阿霉素 ,ADM)、依托泊苷 (VP- 1 6 )、顺铂 (DDP)单药及联合用药连续刺激 ,每种药物分 2个剂量梯度 ,记录细胞每次刺激间隔的时间。应用流式细胞术分别检测 erb B- 2、c- m yc、MDR1、MRP、L RP、ref- 1和 NF- κB的阳性细胞数及平均荧光强度 ,以此推算出不同药物在不同浓度下连续 2～ 3次作用细胞株后以上各蛋白表达的细胞数、平均表达量、总表达量 ,同时设对照组。结果 :随着培养时间的延长 ,各项检测指标的阳性细胞的百分数、平均荧光强度及总荧光强度均呈下降趋势。高剂量各组上述各项指标基本上均随刺激次数的增加呈下降趋势 ,而低剂量各组的检测指标则有升有降 ,无一定规律 ,而 erb B- 2、MDR1、ref- 1和 NF-κB增高。 结论 :小剂量化疗药物连续刺激比大剂量更易诱导肿瘤细胞增殖以及耐药的形成 。Objective:To explore the variation of tumor cell proteins correlated with cell proliferation and chemo-resis-tance after repeated treatment with chemotherapy drugs.Methods:The human lung cancer cell line(LPET-a-2)was repeat-edly treated with chemotherapy drugs:doxorubicin,etoposide,cisplatin and the combination of the3drugs,and each drug was given at2concentrations.The treatment intervals were recorded.ErbB-2,c-myc,MDR1,MRP,LRP,ref-1and NF-κB were tested by flow cytometry.The cells expressing each protein,the mean and total quantity of each protein after each treat-ment were calculated by different drugs at different concentrations.Results:The levels of every protein decreased along with the time of culture.In high-dose group,every item decreased along with the time of treatment.In low-dose group,there was no rule for the item variation with some decreased and some increased.Conclusion:Low-dose anticancer drugs are easier to induce cell proliferation and chemo-resistance than high-dose one,which suggests that adequate chemotherapy should be given in clinical practice.

关 键 词：肺肿瘤 流式细胞术 细胞增殖 抗药性 肿瘤 

分 类 号：R734.2[医药卫生—肿瘤]