摘要
目的观察阿霉素在耐药株LoVo/Adr细胞内的摄入及分布特点,探讨其耐药机制。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-糖蛋白(P-gp)的表达。结果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,相对在胞质中增多;而在敏感LoVo细胞中,阿霉素集中分布在核区,胞质中很少。加入维拉帕米后,不仅LoVo/Adr细胞对阿霉素的蓄积能力显著增强,而且可使阿霉素在LoVo/Adr细胞中的分布恢复到敏感状态。P-gp染色在LoVo细胞株均为阴性,而耐药株LoVo/Adr细胞膜呈强阳性。结论阿霉素在耐药细胞中不仅摄入减少,而且分布异常,主要与P-gp有关,P-gp是药物耐药的机制之一。
Objective To investigateadriamycin(Adr)uptakeanddistributionfeaturesin multidrug-resistantLoVo/Adrcells and explorethedrug-resistancemechanismof the cells.Methods Adr uptakein LoVo/Adrcellswas observedby flow cytometryand the distributionof the drug examinedby fluorescencemicroscope.Immunohistochemicalmethodwas employedto detecttheexpressionof P-glycoprotein(P-gp)by thecells.Results In comparisonwiththatin LoVo/Adrcells,AdrlevelinLoVocellswassignificantlyhigher,butaftertreatmentwithverapamil,theformercellsshowedan increasedAdr level.Adrdistributedmainlyinthenucleusinthedrug-sensitiveLoVocells,withonlya smallquantityinthecytoplasm,while in multidrug-resistantLoVo/Adrcells,significantlyreductionof Adr quantityin the nucleusand relativeincreasein the cytoplasmwereobserved.Inresponseto verapamiltreatment,theAdruptakeinLoVo/Adrcellsincreasedandthedistribution of thedrugwassimilarto thatinsensitivecells.P-gpexpressionwaspositiveinLoVo/Adrcells,whilenegativeinLoVocells.Conclusion AbnormalAdruptakeanddistributionin drug-resistantcellsis relatedto P-gpexpressionwhichis one of the mechanismsformultidrugresistance.
出处
《第一军医大学学报》
CSCD
北大核心
2002年第3期264-266,共3页
Journal of First Military Medical University
