耐药株LoVo /Adr细胞pH与药物分布的关系研究  

Study on relationship between pH in the multidrug resistant LoVo /Adr cell line and distribution of drug

作　　者：马强[1] 张振书[1] 张亚历[1] 赖卓胜[1] 

机构地区：[1]第一军医大学南方医院消化研究所,广州510515

出　　处：《肿瘤》2003年第2期121-123,共3页Tumor

摘　　要：目的　探讨耐药株LoVo /Adr细胞 pH与药物分布的关系。 方法　采用免疫组化法检测P gp的表达 ;在共聚焦显微镜下测细胞内SNAFL calcein AM荧光强度 ,其强度与胞浆的pH成正比 ;利用荧光显微镜观察阿霉素在细胞内的分布。结果　敏感LoVo株细胞P gp染色为阴性 ,而耐药株LoVo /Adr细胞呈强阳性 ;LoVo /Adr细胞内 pH显著高于LoVo细胞 ;LoVo/Adr细胞内阿霉素含量显著低于LoVo细胞 ,且阿霉素在核区分布明显减少 ,相对在胞浆中增多 ;而在敏感LoVo细胞中 ,阿霉素集中分布在核区 ,胞浆中很少。结论　P gp过度表达可能通过影响胞浆的 pH而导致药物在耐药细胞中异常分布 ,可增进其对化疗药物的耐受性 ,是肿瘤细胞发生耐药的原因之一。Objective To investigate relationship between pH in the multidrug resistant LoVo /Adr cell line and distribution of drug. Methods The expression of P-gp was detected by immunohistochemistry. The fluorescence density of SNAFL-calcein-AM which is direct proportional with pH in the cytoplasm was observed by confocal microscope. ADR subcellular distribution was examed by fluorescent microscope. Results P-gp was positive in LoVo /Adr cells, while negative in LoVo cells. The level of pH in the cytoplasm in MDR LoVo /Adr cells was significantly higher than sensitive LoVo cells. The concentration of ADR in LoVo /Adr cells was significantly lower than that in LoVo cells and the distribution of ADR in LoVo /Adr cells significantly decreased in the nucleus and relatively increased in the cytoplasm. The fluorescence of ADR in the drug-sensitive LoVo cells mainly distributed in the nucleus, while a little in the cytoplasm. Conclusion Over expression of P-gp may lead to abnormal distribution of ADR in resistant cells by changing pH level in the cytoplasm. It is one of the mechanisms of multidrug resistance.

关 键 词：多药耐药性 pH 药物分布 LOVO/ADR细胞 

分 类 号：R730.53[医药卫生—肿瘤]