新型环磷酰胺类衍生物9b体内外抗肿瘤作用  

Anti-tumor effects of a novel cyclophosphamide derivate 9b in vivo and in vitro

作　　者：崔朴梅 舒丽[1] 刘菲[1] 杨俊卿 宋杨[2] 孙文娟[1] 

机构地区：[1]重庆市生物化学与分子药理学重点实验室,重庆医科大学药学院药理学教研室,重庆400016 [2]西南大学药学院,重庆400715

出　　处：《药学学报》2014年第1期44-49,共6页Acta Pharmaceutica Sinica

基　　金：中央高校基金科研业务费重点项目(XDJK2010B008);国家"重大新药创制"科技重大专项资助项目(2010ZX09401-306-2-19)

摘　　要：探讨新型环磷酰胺类衍生物4,6-二苯基环磷酰胺(9b)的体内外抗肿瘤活性及其作用机制。体外采用MTT法观察9b对人肝癌细胞株HepG2、人乳腺癌细胞株MCF-7、人白血病细胞株K562的增殖抑制作用;流式细胞仪观察细胞的凋亡率和细胞周期的变化;体内建立肝癌H22荷瘤小鼠模型,观察9b的抑瘤效果。结果表明,9b对体外培养的HepG2、MCF-7、K562细胞有抑制增殖作用,且具有剂量和时间依赖性,9b处理HepG2、MCF-7、K562细胞48 h的IC50分别为32.34、87.07、149.10μmol·L-1;9b使HepG2、MCF-7细胞的G0/G1期细胞和K562细胞的G0/G1和G2/M期细胞明显增加,细胞凋亡率随药物浓度增加亦呈增长趋势;9b对H22实体瘤具有明显的抑制作用。结果提示,9b具有明显的体内外抗肿瘤活性,其抑瘤机制可能与细胞周期改变和诱导肿瘤细胞凋亡相关。This study is to investigate the anti-tumor activities of a novel cyclophosphamide derivate 4, 6- diphenyl cyclophosphamide （9b） in vivo and in vitro, and its possible mechanism of action. The inhibitory effects of 9b on human hepatoma cell line HepG2, human breast carcinoma cell line MCF-7 and human myeloid leukemia cell line K562 were measured by MTT assay in vitro. Cell cycle distribution and apoptotic rate were evaluated by flow cytometry. To evaluate the anti-tumor effect of 9b in vivo, mouse model bearing inoculated H22 tumor was established. The results indicated that 9b could inhibit the proliferation of HepG2, MCF-7 and K562 cells in a dose and time dependent manner. The IC 50 values of 9b were 32.34 μmol.L-1 to HepG2 cells, 87.07 μmol.L-1 to MCF-7 cells and 149.10 ~tmol.L-1 to K562 cells after incubation for 48 h. The results of flow cytometry indicated that after being treated for 48 h with different concentrations of 9b, the ratios of HepG2, MCF-7 cells at the G0/G1 phase and K562 ceils at the G0/G1 phase and G2/M phase increased significantly compared with control group, and the apoptotic rate increased with the increase of the concentration of 9b. 9b could significantly reduce tumor weight of H22 solid tumor mouse model in vivo. To summarize, 9b showed significantly anti-tumor activity in vivo and in vitro, of which the mechanism might be associated with the change of cell cycle distribution and induction of tumor cell apoptosis.

关 键 词：环磷酰胺类衍生物 抗肿瘤活性 细胞周期 细胞凋亡 

分 类 号：R965[医药卫生—药理学]