P-糖蛋白抑制剂HZ08对裸鼠体内肿瘤多药耐药逆转以及对大鼠肝P450酶影响(英文)  

Effects of HZ08,a novel P-glycoprotein inhibitor,on the reversal of P-glycoprotein mediated multidrug resistance in nude mice and cytochrome P-450 activities in rat liver microsomes

作　　者：严方[1] 李运曼[1] 王秋娟[1] 方伟蓉[1] 康恺[1] 张陆勇[2] 

机构地区：[1]中国药科大学生理学教研室,南京210009 [2]中国药科大学新药筛选中心,南京210009

出　　处：《中国药科大学学报》2008年第5期447-452,共6页Journal of China Pharmaceutical University

基　　金：supported by the National High Technology Research and Development Program of China(No.2002AA233071)

摘　　要：目的:考察P-糖蛋白抑制剂HZ08对K562/ADM接种裸鼠体内肿瘤多药耐药的逆转作用及HZ08对大鼠肝P450酶亚型的影响。方法:K562/ADM接种的裸鼠尾静脉注射HZ08和阿霉素4周,与对照组和阳性药组比较瘤重;HZ08与CYP450亚型特异性底物在大鼠肝微粒体中温孵,与对照组比较测定HZ08对于CYP450亚型的影响。结果:HZ08可显著减小裸鼠体内的瘤重,并对大鼠肝微粒体CYP3A4有较弱的抑制作用,对其他P450酶亚型无显著抑制作用。结论:HZ08在裸鼠体内具有较好的逆转P-糖蛋白介导的肿瘤多药耐药的作用,并且在体外实验中对P450酶具有较小的影响。Aim： To evaluate the effects of HZ08, a novel P-glycoprotein inhibitor, on reversing tumor resistance of K562/ADM to adriamycin in nude mice and on the activities of cytochromes P-450 （CYP） isoforms. Methods： Nude mice bearing K562/ADM were injected at different doses of HZ08 with adriamycin for 4 weeks. The tumor weights of HZ08 treatment groups were determined and compared to those of the control and positive groups. In addition, the effects of HZ08 were examined on CYP isoforms-mediated metabolism of specific substrates by CYP isoforms in rat liver microsomes in the presence or absence of HZ08. Results： The tumor weights of HZ08 treat- ment groups were significantly decreased and HZ08 was a relatively potent inhibitor of CYP3A4, with no significant effects on other isoforms tested. Conclusion： HZ08 has potent effects on reversing P-glycoprotein mediated tumor multidrug resistance in vivo with little influence on cytochrome P-450 activities of rat liver.

关 键 词：HZ08 肿瘤多药耐药 裸鼠 P-糖蛋白抑制剂 肝P450酶 

分 类 号：R965[医药卫生—药理学] R730.5[医药卫生—药学]