mdr1介导的获得性多药耐药性在胃癌细胞SGC7901的自然逆转

目的:探讨mdr1介导的获得性多药耐药在胃癌细胞SGC7901的自然逆转情况.方法:将培养细胞分为SGC7901、加长春新碱(VCR)的SGC7901/VCR和停VCR 6个月的SGC7901/VCR(设为SGC7901/VCR-)3组,用RT-PCR和原位杂交检测mdr1 mRNA的表达,免疫印迹和免疫组化检测P-gp的表达,流式细胞仪检测阿霉素在细胞内的蓄积和潴留,MTT法检测细胞对化疗药物的敏感性.结果:SGC7901/VCR-组mdr1 mRNA和P-gp表达水平介于SGC7901和SGC7901/VCR之间.SGC7901/VCR-阿霉素蓄积和潴留均高于SGC7901/VCR,低于SGC7901(P<0.05).SGC7901/VCR-对化疗药物的IC50小于SGC7901/VCR,大于SGC7901(P<0.01);对DDP和ADR的耐药指数低于SGC7901/VCR(P<0.05).结论:停化疗药物6个月后,胃癌耐药细胞亚系SGC7901/VCR的多药耐药性降低,但未降到亲本SGC7901水平.

The Natural Reversal of Acquired mdr1 Gene-dependent Multidrug Resistance in Gastric Cancer Cells SGC7901

Objective: To study the natural reversal of the acquired mdr1 gene-dependent multidrug resistance in gastric cancer SGC7901 cells.Methods: The cultured cells were divided into 3 groups: SGC7901 group cells;SGC7901/VCR group cells cocultured with vincristine(VCR)and SGC7901/VCR~-group cells cultivated with no VCR for six months in the SGC7901/VCR cells.The expression of mdr1 mRNA was detected by RT-PCR and hybridization in situ.The expression of P-gp was detected by Western blotting and immunohistochemistry.The accumulation and retention of intracellular adriamycin(ADR) were examined by flowcytometry.The cell sensitivity to chemotherapeutic drugs was demonstrated by MTT.Results: The expression level of mdr1 mRNA and P-gp in the SGC7901/VCR~-cells lay between that of the SGC7901/VCR and the SGC7901 cells.The accumulation and retention of ADR in the SGC7901/VCR~-cells were higher than those in the SGC7901/VCR but lower than those in the SGC7901 cells(P<0.05).The IC50 values of the SGC7901/VCR~-cells to chemotherapeutic drugs were less than those of the SGC7901/VCR but more those of the SGC7901 cells(P<0.01).The drug resistance index of the SGC7901/VCR~-cells was lower than that of the SGC7901/VCR cells(P<0.05).Conclusions: After the SGC7901/VCR cells cultivated with no VCR for six months,the mdr1 gene-dependent multiple drug resistance declined and yet couldn't approach up to the level of its parental SGC7901 cells.