摘要
目的 观察PKC对耐药LoVo/Adr细胞阿霉素摄入及分布的影响 ,探讨其与耐药的关系。方法 采用流式细胞术检测阿霉素在细胞中的摄入 ;利用荧光显微镜观察阿霉素在细胞内的分布 ;采用免疫组化法检测P gp的表达。结果 P gp染色 :Lo Vo细胞株均为阴性 ,而耐药株LoVo/Adr细胞膜呈强阳性 ;LoVo/Adr细胞内阿霉素含量显著低于LoVo细胞 ,加入PMA后 ,Lo Vo/Adr细胞内ADR含量进一步减少 ;加入SP后 ,LoVo/Adr细胞内ADR含量明显升高。在敏感LoVo细胞中 ,阿霉素集中分布在核区 ,胞浆中很少 ;而在LoVo/Adr细胞中 ,阿霉素核区分布明显减少 ,相对在胞浆中增多 ,加入PMA或SP ,均不能改变阿霉素在细胞中的分布。结论 阿霉素在耐药细胞中不仅摄入减少 ,而且分布异常 ,PKC可能是通过影响耐药细胞对阿霉素的摄入而不是药物分布来调节MDR。
Objective To observe the effects of protein kinase C on the uptake and distribution of ADR in the multidrug resistant LoVo/Adr cells of colo rectal carcinoma. Methods The uptake of ADR in cells was studied by flow cytometry and the distribution of ADR in cells was examined by fluorescent microscope. The expression of P gp was detected by immunohistochenical method. Results P gp stain was negative in LoVo cells, but intensively positive in LoVo/ADR cells. The concentration of ADR was in LoVo/Adr cells was significantly lower than that in LoVo cells. The uptake of ADR was reduced after treating with PMA in LoVo/Adr cells, but was significantly increased after treating with SP. The fluorescence of ADR in the drug sensitive LoVo cells was mainly distributed in the nucleus, but only a little in the cytoplasm. While the distribution of ADR in LoVo/Adr cells markedly decreased in the nucleus and relatively increased in the cytoplasm. Neither PMA nor SP could change the distribution of ADR in LoVo/Adr cells. Conclusion Not only the uptake of ADR decreased but also the distribution of ADR was abnormal in resistant cells. PKC might modify multidrug drug resistance by effecting on the uptake but not on the distribution of ADR in resistance cells.
出处
《肿瘤》
CAS
CSCD
北大核心
2002年第4期303-304,321,F003,共4页
Tumor
