17-DMAG对人结直肠癌裸鼠移植瘤微血管形成的抑制作用

Inhibition of 17-DMAG on microvessel formation in nude mice with transplanted human colorectal cancer

目的探讨17-二甲基胺乙基-17-去甲氧基格尔德霉素(17-DMAG)对结直肠癌微血管生成的抑制作用。方法 24只BALB/C-nu/nu裸鼠用于建立裸鼠结直肠癌移植瘤模型,并将其随机分为17-DMAG、5-氟尿嘧啶(5-FU)及对照组各8只,分别腹腔注射17-DMAG、5-FU、生理盐水,4周后测量裸鼠移植瘤体质量、体积,采用免疫组织化学染色法检测肿瘤组织中微血管密度(MVD)和血管内皮生长因子(VEGF),采用蛋白免疫印迹法检测VEGF。比较3组结果。结果 17-DMAG组、5-FU组移植瘤体质量、体积与对照组比较差异均有统计学意义(P均<0.05);17-DMAG组MVD、VEGF水平均低于5-FU组与对照组(P均<0.05),而5-FU组与对照组的MVD、VEGF水平比较差异无统计学意义(P均>0.05)。结论 17-DMAG可通过下调VEGF的表达减少结直肠癌组织中新生血管的生成进而抑制肿瘤的生长。

Objective To observe the inhibition of 17-dimethylaminoethylamino-17 demethoxy- geldanamycin （17-DMAG） on microvessel formation and tumor growth in nude mouse mode with implanted colorectal cancer. Methods Twenty-four BALB/C-nu/nu nude mice were developed into tumor models and then randomly divided into 3 groups ： 17-DMAG group （ n = 8 ）, 5-fluorouracil group （ n = 8 ） and control group （ n = 8 ）. Four weeks after treatment, tumor volume and weight in all groups were evaluated. At the meantime, mirovessel density （MVD） and vascular endothelial growth factor （VEGF） in the tumors were detected by immunohistochemical staining. The expression of VEGF was determined by western blotting. The results of all groups were compared. Results The tumor weight and size in both 17-DMAG group and 5-FU group were significantly less than those in control group （ P 〈 0. 05 ）. MVD and VEGF expression in 17-DMAG group were lower than those of 5-FU group and control group （ P 〈 0. 05 ）. There were no significant differences in MVD and VEGF expression between 5-FU group and control group （P 〉 0. 05 ）. Conclusions 17-DMAG suppresses the angiogenesis of colorectal cancer by down regulating VEGF expression and then inhibits tumor growth.