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双嘧达莫对胃癌多药耐药的逆转实验研究 被引量:7

Experimental study of reversion effect of dipyridamole on multidrug resistance in gastric cancer cell line
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摘要 目的 研究双嘧达莫对胃癌细胞多药耐药的逆转作用。方法 逐渐递增长春新碱浓度诱导胃癌细胞株SGC790 1产生多药耐药性 (SGC790 1r)。以双嘧达莫为逆转剂 ,MTT法测定抗癌药对肿瘤细胞的杀伤作用 ;激光全聚焦显微镜测定肿瘤细胞内柔红霉素和钙离子荧光强度。结果 胃癌SGC790 1r细胞对长春新碱、柔红霉素、丝裂霉素及顺铂的耐药性分别为SGC790 1细胞的 4.46倍、14.95倍、2 1.2 0倍和 16 .0 6倍。经双嘧达莫(5 0 μg/ml)预处理 1h后 ,柔红霉素对SGC790 1r的半数抑制浓度明显下降 (P <0 .0 5 )。SGC790 1r在静息时细胞内Ca2 + 明显高于药物敏感的母细胞株SGC790 1;细胞内柔红霉素的荧光强度亦明显降低 (P <0 .0 5 )。双嘧达莫 (5 0 μg/ml)使SGC790 1r细胞内Ca2 + 明显下降 ,柔红霉素荧光强度显著提高 (P <0 .0 5 ) ;对药物敏感细胞SGC790 1无明显作用。结论 双嘧达莫增加柔红霉素在耐药细胞内的积累 ,部分逆转SGC790 1r的耐药性。 Objective To study the reversion effect of dipyridamole on multidrug resistance in gastric cancer. Methods A multidrug resistant gastric cancer cell line SGC7901r was induced by an escalating concentration of vincristine, and dipyridamole was used as a reverser. The cytotoxicity of anti cancer drugs was detected by MTT. The intensities of intracellular fluorescence of daunorubicin and Ca 2+ were detected by laser confocus microscope. Results Comparing to SGC7901, the resistance of SGC7901r to Vincristine, Daunorubicin, Cisplatin and Mitomycin were 4.46, 14.95, 21.20 and 16.06 folds higher, respectively; the intracellular Ca 2+ of SGC7901r was significantly increased, but the intracellular fluorescence intensity of Daunorubicin was significantly decreased ( P <0.05). Being pretreated by dipyridamole (50 μg/ml) within 1 hour, SGC7901r showed a significant decrease of IC 50 to Daunorubicin. The treatment of dipyridamole in the above dosage could decrease the intracellular Ca 2+ (P<0.05), on the contrary, it could increase the intracellular fluorescence intensity of Daunorubicin ( P <0.05). However this treatment had no effect on drug sensitive SGC7901 cell line. Conclusion Dipyridamole enhances the accumulation of Daunorubicin in gastric cancer cells,hence,it can partially reverse the resistance of SGC7901 cell line.(Shanghai Med J,2000,23∶286 289)
出处 《上海医学》 CAS CSCD 北大核心 2000年第5期286-289,共4页 Shanghai Medical Journal
关键词 胃癌 多药耐药性 双嘧达莫 逆转实验 Gastric cancer Multidrug resistance Dipyridamole Reversion effect
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