鸦胆子油乳具有多药耐药逆转和拓扑异构酶Ⅱ抑制作用  

Reversal of multidrug resistance and inhibition of DNA topoisomerase Ⅱ by emulsion of seed oil of Brucea Javanica

作　　者：汤涛[1] 蒙凌华[1] 陈陵际 丁健[1] 

机构地区：[1]中国科学院上海药物研究所肿瘤药理组,上海200031

出　　处：《中国药理学通报》2001年第5期534-539,共6页Chinese Pharmacological Bulletin

摘　　要：目的　研究鸦胆子油乳体外对多药耐药细胞株的作用和对拓扑异构酶 (topoisomerase ,TOPO)活性的影响。 方法　MTT法测定鸦胆子油乳体外对敏感和耐药细胞株的杀伤作用 ;TOPOⅠ介导的负超螺旋 pBR3 2 2解旋反应和TOPOⅡ介导的kDNA去连环反应检测鸦胆子油乳对TOPOⅠ和TOPOⅡ催化活性的影响。结果　鸦胆子油乳浓度为 0 0 2 5g·L-1时能在一定程度上逆转K5 62 /A0 2、MCF 7/ADM和KB/VCR等细胞的耐药性。鸦胆子油乳能抑制TOPOⅡ介导的kDNA去连环作用 ,浓度为 0 3 1g·L-1时鸦胆子油乳可部分抑制TOPOⅡ酶活力 ,浓度为 2 5g·L-1则完全抑制TOPOⅡ酶活力 ;对TOPOⅠ介导的pBR3 2 2解旋作用无影响 ,对DNA也无直接作用。结论　鸦胆子油乳对多药耐药有一定的逆转作用 ,并能明显抑制TOPOⅡ的活性。AIM To explore the reversal effect of multidrug resistance (MDR) and the influence on topoisomerase (TOPO) activity by emulsion of seed oil of Bbrucea Javanica (ESOBJ) in vitro . METHODS Cytotoxic effects of ESOBJ against sensitive and resistance tumor cells were deter mined by MTT assay. Influences of ESOBJ on the catalytic activities of TOPO Ⅰ and TOPO Ⅱ were measured by TOPO Ⅰ mediated negatively super coiled pBR322 relaxation and TOPOⅡ mediated kDNA decatenation. RESULTS 0 025 g·L -1 of ESOBJ could reverse MDR in various MDR cell lines such as K562/A02?MCF 7/ADM and KB/VCR. DNA TOPO Ⅱ mediated kDNA decatenation experiment showed marked inhibitory action of ESOBJ on TOPO Ⅱ activity at the concentration of 0 31 g·L -1 and TOPO Ⅱ activity was totally inhibited by ESOBJ at the concentration of 2 5 g·L -1 . On the other hand, ESOBJ exhibited no influence on DNA TOPO I mediated pBR322 relaxation and on DNA directly. CONCLUSION ESOBJ could reverse MDR to a certain extent in vitro , and inhibit the activity of TOPO Ⅱ significantly.

关 键 词：鸦胆子油乳 多药耐药 DNA拓扑异构酶 抗癌作用 

分 类 号：R979.1[医药卫生—药品] R73－36[医药卫生—药学]