Effects of HZ08,a novel P-glycoprotein inhibitor, on the reversal of P-glyco-protein mediated multidrug resistance in nude mice and cytochrome P-450 ac-tivities in rat liver microsomes
- VernacularTitle: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
- Author:
Fang YAN
;
Yunman LI
;
Qiujuan WANG
;
Weirong FANG
;
Kai KANG
;
Luyong ZHANG
- Publication Type:Journal Article
- Keywords:
HZ08;
tumor muhidrug resistance;
nude mice;
P-glycoprotein inhibitor;
cytochrome P450 enzyme CLC Number
- From:
Journal of China Pharmaceutical University
2008;(5):447-452
- CountryChina
- Language:Chinese
-
Abstract:
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 (GYP) 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 GYP isoforms-mediated metabolism of specific substrates by GYP isoforms in rat liver microsomes in the presence or absence of HZ08. Results: The tumor weights of HZ08 treatment 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 rive with little influence on cytoehrome P-450 activities of rat liver.
