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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 investigate the reversal effect of P-glycoprotein inhibitor HZ08 on multidrug resistance in K562 / ADM inoculated nude mice and the effect of HZ08 on rat liver P450 subtypes. Methods: K562 / ADM inoculated nude mice tail vein injection of HZ08 and doxorubicin 4 weeks, compared with the control group and the positive drug group tumor weight; HZ08 and CYP450 subtype specific substrate incubated in rat liver microsomes, and The control group compared the effect of HZ08 on CYP450 subtypes. Results: HZ08 could significantly reduce the tumor weight in nude mice and had a weaker inhibitory effect on the CYP3A4 of rat liver microsomes and no significant inhibition on other P450 subtypes. CONCLUSION: HZ08 has good effect of reversing P-glycoprotein-mediated multidrug resistance in nude mice and has less effect on P450 enzyme in vitro.