胃癌多药耐药细胞药物积累的异常

Abnormal drug accumulation in multidrug resistant gastric carcinoma cells

目的研究胃癌多药耐药细胞与敏感细胞细胞内药物浓度的差异.方法通过逐渐递增化疗药物长春新碱浓度诱导胃癌细胞株产生多药耐药性.应用[3H]长春新碱方法测定多药耐药细胞对化疗药物的摄取;利用抗癌药柔红霉素在肿瘤细胞内的自发荧光,用激光共聚焦显微镜观察柔红霉素在细胞内的分布,及撤去柔红霉素后的不同时间点细胞内柔红霉素荧光强度.结果柔红霉素在细胞内的荧光主要集中在细胞核,在细胞质内亦有较少的荧光显示.多药耐药细胞内[3H]长春新碱的浓度明显低于亲代细胞;撤去柔红霉素后各个时间点多药耐药细胞内柔红霉素的荧光强度亦均低于亲代细胞.结论胃癌多药耐药细胞株对细胞毒药物的摄取低于敏感细胞,外排高于敏感细胞,从而导致药物在细胞内的浓度降低,细胞毒作用减弱.

AIM To study the difference in intracellular concentration of drug between multidrug resistant cells and drug sensitive cells of gastric carcinoma. METHODS Multidrug resistant gastric carcinoma cell sublines were established by a stepwise increase of concentration of vincristine in media. The uptake of drug was measured by isotope liquid scintillation counter. Laser confocus microscope was used to study the intracellular distribution of daunorubicin and fluorescent intensity of daunorubicin in drug- resistant and drugsensitive cells after incubated in drug-free media for various time periods. RESULTS Fluorescent of daunorubicin was mainly contained in the nuclei of both sensitive and resistant cells. The fluorescent intensity of daunorubicin in drugresistant cells was lower after incubated in drug-free media for various time periods. CONCLUSION The multidrug resistant gastric cells present a lower rate of drug uptake, and the rate of efflux drug was greater than the sensitive parent cell lines, resulting in the decrease of the intracellular concentration of anticancer drug in multidrug resistant calls, and the cytotoxity of drug.