摘要
目的 建立肿瘤耐药机制研究及筛选抗肿瘤药物的体外实验模型。方法 应用药物连续作用并逐步提高药物浓度的剂量递增法及软琼脂细胞克隆技术 ,用拒染法测定药物的细胞毒作用 ,建立了一株对顺铂 (DDP)具有 40倍耐药性的L12 10细胞亚系 (L12 10 /DDP40 )。结果 DDP耐药细胞亚系在倍增时间、集落形成率、细胞周期、DNA指数和细胞形态等方面基本保持了亲代细胞 (L12 10 )的生物学特性。耐药细胞亚系在加药状态下冻存半年后复苏其耐药性仍然存在 ,解除药物作用后 5mon其耐药性仍维持原有水平。耐药细胞亚系对卡铂、丝裂霉素、噻替派、甲氨蝶呤、长春新碱和氮芥具有不同程度的交叉耐药性 ,对三尖杉酯碱和阿霉素无交叉耐药性 ,对阿糖胞苷和氟尿嘧啶仍较敏感。结论 DDP耐药性L12 10细胞亚系的建立 ,为深入研究肿瘤细胞耐药机制、寻找逆转耐药的措施提供了较好的体外实验模型。
AIM To establish the expermental model in vitro for the study of mechanism of antitumor drug resistance and the screening of antitumor drug. METHODS By continuously exposing cells to gradually increasing concentration of drug and agar cell colony forming technique, using dye exclusive method for determing cytotoxic effect, a murine leukemia L1210 cell subline were established,which exhibited 40 fold resistance to Cis diamminedichloro platinum(DDP). RESULTS The doubling times, plate efficiency, cell cycle, DNA index and cell morphology of DDP resistant L1210 subline were similarto those of its parant cell line. When the cell subline was stored with DDP at -196℃ for 6 months and then was recovered, its characterization of antitumor drug resistance was still maintained to a period of 5 months without DDP. DDP resistant L1210 subline was characterized with cross resistance to Carboplatin, Mitomycin, Thio Tepa, Methotrexate, Vincristin and Mustine Hydrochloride, but with no cross resistance to Harringtonine and Adriamycin. It was seemed more sensitive to Cytarabine and Fluorouracil. CONCLUSION DDP resistant L1210 subline is a good experimental model in vitro for the study of mechanism of antitumor drug resistance and the screening of antitumor drug.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2000年第6期708-710,共3页
Chinese Pharmacological Bulletin
基金
国家重点基础研究发展规划项目!NoG19990 5 440 1
关键词
顺铂
耐药性
L1210细胞亚系
抗肿瘤药
Cis diamminedichloro platinum
resistance
L1210 cell subline
tumor
