环磷酰胺在动物模型体内抗肿瘤影响及抑瘤机制的研究

摘要

Objective To study the effect arid mechanism of cyclophosphamidc (CTX) on antiiumor in animal mode]. Methods The solid lumor model and aseitic tumor model were esia blushed by ubeutaneous Injection of the Kunming mouse with sarcomas (S180) and Intraperitoncal injection with marine hcpatocarcinoma (H22j respectively, meanwhile CTX was given. After that, the changes of tumor and mouse-survival were recorded. The expression of Bel-2, VEGF, P53 and P21 were tested by western blot. Results Compared with the control group, the tumor was significantly lighter (the antitu-mor 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.%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%;环磷酰胺町明显诱导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.