KB细胞耐药株的建立及其耐药机制的探讨  

VINCRISTINE-RESISTANT HUMAN KB CELL LINE AND MECHANISM OF MULTIDRUG RESISTANCE

作　　者：张晓红[1] 张福荣[1] 籍秀娟[1] 李占荣[1] 

机构地区：[1]中国医学科学院,中国协和医科大学药物研究所

出　　处：《药学学报》1994年第4期246-251,共6页Acta Pharmaceutica Sinica

摘　　要：用对长春新碱（ＶＣＲ）敏感的ＫＢ细胞为亲本，通过诱变剂甲基磺酸乙酯刺激，然后在培养液中加入浓度递增的ＣＶＲ，得到耐药细胞株ＫＢＶ２００。此细胞株对ＶＣＲ的耐受程度约为ＫＢ细胞的１７５倍。对其它抗肿瘤药物如紫杉醇、秋水仙碱和阿霉素等也有不同程度的交叉耐药性。进一步研究表明，ＫＢＶ２００对３Ｈ－ＶＣＲ的蓄积明显减少，且耐药基因（ｍｄｒ１）表达增加。钙通道阻滞剂维拉帕米（Ｖｅｒ）可增加ＫＢＶ２００对３Ｈ－ＶＣＲ的蓄积和对ＶＣＲ的敏感性。这些结果提示，ＫＢＶ２００耐药的机制可能是由于ｍｄｒ１基因表达增加，产生过量的ｐ－糖蛋白，使药物外排增多所致。A multidrug-resistant(mdr)clone of human cancer KB cells was isolated by step-wise selection on exposure to increasing doses of vincristine. The final clone ,KBV200 ,obtained afterethylmethane sulfonate(EMS)mutagenesis showed 175-fold higher resistance to vincristine than didKB crlls. The cells were also cross-resistant to taxol, colchicine and adriamycin. Cellular accumlation of vincristine in KBV200 was decreased to less than one-fifth of that in KB.To determine the presence of mdr 1 mRNA in KBV200 and KB ,total cellular RNAs from each cell linewere analyzed by means of slot blot hybridization The result showed that the mdr 1 gene had beenhighly expressed in KBV200. In addition , verapamil,a calcium channel blockers ,was shown to increase VCR accumulation inKBV200 and reverse the vincristine resistance. All these results demonstrate that the mechanism ofKBV200 cell resistance to multiple drugs resulted from increased expression of mdr 1 gene and brought about over production of P-glycoprotein and increased the efflux of drugs.

关 键 词：KB细胞 耐药株 长春新碱 MDR1基因 

分 类 号：R979.1[医药卫生—药品]