环磷酰胺在动物模型体内抗肿瘤影响及抑瘤机制的研究  

Study of the effect and mechanism of Cyclophosphamide on antitumor in animal model

作　　者：迟淑萍[1] 白冰珂[1] 谢进[1] 陈红鸽[1] 杜丽[1] 由莉越[1] 程云[1] 

机构地区：[1]解放军302医院药学部,北京100039

出　　处：《中国医药导报》2012年第14期20-22,共3页China Medical Herald

基　　金：国家科技重大专项重大新药创制课题(2009ZX09103)

摘　　要：目的探讨环磷酰胺(CTX)在动物模型体内抗肿瘤影响及抑瘤机制。方法建立小鼠实体瘤模型和腹水瘤模型:分别在昆明系小鼠皮下接种S180肉瘤细胞、腹腔接种鼠源性H22肝癌细胞,同时给予环磷酰胺处理小鼠,其后观察各组肿瘤生长大小,小鼠存活率的变化;应用Western blot技术检测凋亡抑制基因(Bcl-2)、血管内皮细胞生长因子(VEGF)含量、抑癌基因P53及P21的蛋白表达。结果环磷酰胺组肿瘤重量明显低于模型组(P<0.05),其抑瘤率为88.55%;小鼠存活天数均较模型组长,其生命延长率为57.73%;环磷酰胺可明显诱导P53的表达,抑制BCL-2的表达,从而促进肿瘤细胞的凋亡,但对P21没有作用;对瘤体组织中VEGF蛋白表达水平亦有抑制作用。结论环磷酰胺可通过激活抑癌基因P53,抑制抗凋亡基因Bcl-2和促血管生成因子VEGF等多种途径,发挥抗肿瘤活性,为抗肿瘤动物模型尤其为调节抗肿瘤相关基因表达方面的阳性药物对照提供重要的实验依据。Objective To study the effect and mechanism of cyclophosphamide（CTX） on antitumor in animal model.Methods The solid tumor model and ascitic tumor model were esta blushed by ubcutaneous injection of the Kunming mouse with sarcomas（S180） and intraperitoneal injection with murine-hepatocarcinoma（H22） respectively,meanwhile CTX was given.After that,the changes of tumor and mouse-survival were recorded.The expression of Bcl-2,VEGF,P53 and P21 were tested by western blot.Results Compared with the control group,the tumor was significantly lighter（the antitumor rate was 88.55%） and mice survived longer（the increase of life span was 57.73%）.CTX could significantly induce the expression of P53 and inhibit the expression of BCL-2,but was invalid to P21.CTX could also inhibit the expression of VEGF.Conclusion CTX can play the antitumor role by activating the expression of Bcl-2,VEGF and P53,which give implications for development of animal model and drug in antitumor field.

关 键 词：环磷酰胺 WESTERN BLOT S180肉瘤 H22肝癌细胞 抗肿瘤相关基因 

分 类 号：R969.4[医药卫生—药理学]