柔红霉素-白蛋白交联物逆转多药耐药KB/VCR细胞株对柔红霉素的耐药性  

multidrug resistant KB/VCR cells to daunorubicin

作　　者：吴达龙[1,2] 李盟军[1,2] 高洪志[1,2] 吴德政 

机构地区：[1]军事医学科学院附属医院临床药理科 [2]解放军八一医院肿瘤内科

出　　处：《中国药理学与毒理学杂志》1997年第1期54-58,共5页Chinese Journal of Pharmacology and Toxicology

摘　　要：将柔红霉素（Ｄａｕ）与牛血清白蛋白（ＢＳＡ）交联，以克服耐长春新碱（ＶＣＲ）的ＫＢ细胞株（ＫＢ／ＶＣＲ）对Ｄａｕ的耐药性．Ｄａｕ抑制ＫＢ和ＫＢ／ＶＣＲ细胞生长的ＩＣ５０分别为３．３μｇＬ－１和０．２６ｍｇＬ－１．ＫＢ／ＶＣＲ细胞对Ｄａｕ的耐药性是ＫＢ细胞的７９倍．反转录聚合酶链式反应结果显示，ＫＢ／ＶＣＲ细胞有很高水平的ｍｄｒ－１基因表达．Ｄａｕ－ＢＳＡ交联物和Ｄａｕ杀伤ＫＢ／ＶＣＲ细胞的ＥＣ５０分别是１２μｇＬ－１（指其中Ｄａｕ含量）和０．２４ｍｇＬ－１，即Ｄａｕ－ＢＳＡ对ＫＢ／ＶＣＲ细胞的细胞毒作用是Ｄａｕ的２０倍．药物蓄积实验显示，使用Ｄａｕ－ＢＳＡ时，ＫＢ／ＶＣＲ细胞内Ｄａｕ蓄积量较使用Ｄａｕ者增加１．４倍（２４ｈ时）；药物外排实验显示，加入Ｄａｕ时，Ｄａｕ迅速从ＫＢ／ＶＣＲ细胞排出，而使用Ｄａｕ－ＢＳＡ时Ｄａｕ能在ＫＢ／ＶＣＲ细胞内长时间维持较高浓度．结果提示，Ｄａｕ与ＢＳＡ交联后，能克服多药耐药细胞对Ｄａｕ的耐药性．Daunorubicin (Dau) bovine serum albumin (BSA) conjugate (Dau BSA) via a glutaraldehyde bridge was used to overcome tumor cells resistance to Dau. A multidrug resistant variant of KB cell line (KB/VCR) was established in vitro by repeat exposure of the cells to vincristine. KB/VCR cells were 79 times more resistant to Dau than parent KB cells. There was high expression of mdr 1 gene in KB/VCR cells. EC 50 of Dau for killing KB/VCR cells was 0.24 mg·L 1 and that ofDau BSA was 12 μg·L 1 (equivalent to free Dau). Dau BSA was 20 fold more cytotoxic to KB/VCR cells than equivalent free Dau. The measurements of drug uptake showed that the intracellular Dau concentration following the treatment of KB/VCR cells with Dau BSA was 2.4 times of that in the cells treated with Dau. The analysis of drug efflux showed that after the preincubation of KB/VCR cells with Dau, cellular Dau was effluxed rapidly from the cells, while a relatively high concentration of Dau was kept for longer time in KB/VCR cells treated with Dau BSA. These results indicate that it may be possible to overcome multidrug resistance by chemically modified Dau, such as by conjugation of the drug with proteins.

关 键 词：抗药性 柔红霉素 KB细胞 多药抗药性 

分 类 号：R979.14[医药卫生—药品]