mdr1及bcr-abl阳性白血病细胞对酪氨酸激酶抑制剂STI571耐药的逆转  

The Reverse Effect on Drug-Resistance against Tyrosine Kinase Inhibitor STI571 in mdr1 and bcr-abl Positive Leukemic Cells

作　　者：陈莉[1] 王健民[1] 许小平[1] 高磊[1] 费新红[1] 楼敬伟[1] 黄正霞[1] 

机构地区：[1]第二军医大学附属长海医院血液科,上海200433

出　　处：《中国实验血液学杂志》2003年第6期600-603,共4页Journal of Experimental Hematology

基　　金：国家自然科学基金资助项目 编号 3 9770 3 3 0

摘　　要：为了探索bcr abl和mdr1阳性的白血病细胞对酪氨酸激酶抑制剂STI5 71是否有交叉耐药及其逆转方法 ,采用MTT法检测STI5 71对K5 6 2 n/VCR细胞的抑制作用 ,采用多药耐药逆转剂环孢菌素A(CsA)、他莫西芬(TAM)、α 干扰素 (IFN α)单用及CsA与IFN α联合应用研究对STI5 71耐药的逆转作用。结果表明 :K5 6 2 n/VCR细胞对STI5 71有交叉耐药性。CsA ,IFN α ,TAM 3种逆转剂对其均有不同程度的逆转作用 ,逆转倍数分别为 5 18倍、1.6 7倍及 1.82倍。而半量CsA +IFN α对K5 6 2 n/VCR细胞STI5 71的逆转倍数为 34.87倍。结论 :多药耐药基因mdr1的扩增可以导致bcr abl阳性白血病细胞对STI5 71的耐药。多药耐药逆转剂CsA ,TAM和IFN α对STI5 71耐药有明显的逆转作用 ,CsA与IFN α半量联合对K5 6 2 n/VCR细胞的杀伤作用显著超过全量CsA或IFN α的逆转耐药作用。本研究结果提示对STI5 71发生耐药的患者加用CsA和IFN α ,可能会提高其疗效。To explore the possibility of leukemia cell line of both bcr abl and mdr 1 positive were cross resistant to tyrosine kinase inhibitor STI571 and its reversal way, the inhibitory effect of STI571 on K562 n/VCR cells was detected with MTT method and reverse effects of CsA, TAM, IFN α and CsA cominated with IFN α were observed. The results showed that K562 n/VCR cell line expressing bcr abl and mdr1 positive was resistant to STI571, and could be reversed by 5.18, 1.82 and 1.67 fold respectively, when treated with CsA, TAM, and IFN α. It could be reversed by 34.87 fold with combination of half dose CsA and IFN α. In conclusion, amplification of mdr1 gene may contribute to drug resistance of bcr abl positive leukemic cells against STI571. The reversal agents, CsA, TAM and IFN α show obviously reverse effects on drug resistance. The combination of half dose of both CsA and IFN α display stronger effect than the full dose of either.

关 键 词：MDRL基因 BCR-ABL基因 白血病 酪氨酸激酶 治疗 

分 类 号：R733.7[医药卫生—肿瘤]