17-丙烯胺-17-去甲氧格尔德霉素对大鼠嗜铬细胞瘤裸鼠移植瘤的抑制作用  

The inhibitory effect of 17-allylamino-17-demethoxygeldanamycin on the implanted rat malignant pheochromocytoma nude mice

作　　者：朱奇[1] 祝宇[1] 徐云泽[1] 陈东宁[1] 徐烈雨 张翀宇[1] 赵菊平[1] 吴瑜璇[1] 沈周俊[1] 宁光[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院泌尿外科,上海200025

出　　处：《现代泌尿外科杂志》2014年第5期333-336,共4页Journal of Modern Urology

基　　金：国家自然科学基金(No.81272936);上海市科委医学引导项目(No.134119a2700)

摘　　要：目的通过观察热休克蛋白90(HSP90)抑制剂17-丙烯胺-17-去甲氧格尔德霉素(17-AAG)对大鼠嗜铬细胞瘤裸鼠移植瘤生长的影响,探讨17-AAG对大鼠嗜铬细胞瘤肿瘤生长和血管生成的抑制作用。方法用大鼠嗜铬细胞瘤细胞PC12接种于裸鼠皮下,建立移植瘤模型,15d后将荷瘤裸鼠随机分为2组,每组12只,分别为实验组(腹腔注射17-AAG 40mg/kg)和对照组(腹腔注射生理盐水10mL/kg),用药3周。第4周后测量裸鼠移植瘤的体积变化以及裸鼠的生存时间。采用免疫组化方法检测肿瘤组织中HSP90、血管内皮生长因子(VEGF)的表达,采用Western blotting法检测肿瘤组织中HSP90、VEGF的表达。结果第4周时,移植瘤体积的对照组和实验组分别为(5 070.13±630.42)mm3和(2 218.80±336.29)mm3,两组移植瘤体积存在显著性差异(P<0.05);平均生存时间对照组和实验组分别为(26.0±5.1)、(42.7±7.5)d,用Kaplan-Meier、Log-Rank方法分析两组的生存函数的差异有统计学意义(P<0.05)。免疫组化显示HSP90在对照组中呈高表达(10/12,83.3%),在实验组中呈低表达(4/12,33.3%);VEGF在对照组中呈高表达(11/12,91.7%),在实验组中呈低表达(4/12,33.3%);实验组肿瘤组织的HSP90、VEGF表达明显低于对照组(P<0.05)。Western blotting法也显示两种蛋白在实验组上的表达明显低于对照组(P<0.01)。结论 17-AAG对大鼠嗜铬细胞瘤裸鼠移植瘤有明显抑制作用,并可降低肿瘤组织中HSP90和VEGF的表达。Objective To investigate the effect of heat shock protein 90 （HSP90） inhibitor 17-allylamino-17-demethoxy- geldanamycin （17-AAG） in the implanted rat malignant pheochromocytoma nude mice and to explore the inhibitory mechanism of 17-AAG on the tumor growth and angiopoiesis of malignant pheochromocytoma. Methods Rat malignant pheochromocy- toma xenograft model was created by implanting PC12 cells in the left flank of nude mice. After 15 days, the nude mice were randomly divided into two groups： the experiment group （receiving 40 mg/kg 17-AAG） and the control group （treated with 10 mL/kg NS）. After 3 weeks＇ treatment, the tumors were obtained, then the tumor volumes were measured in the 4th week. During this time, the change of tumor volumes was observed and the survival time was recorded. The expressions of HSP90 and vascular endothelial growth factor （VEGF） were detected by immunohistochemical staining and western blotting. Results In the 4 th week, the tumor size in the experiment group was （2 218.80±336.29）mma , while that in the control group was （5 070. 13±630.42）mm3. The growth of tumor in the experiment group was slower than that in the control group, which had a statistical significance. The average survival time of the experiment group was （42.7 ± 7.5）days, while that in control group was （26.0±5.1）days, with statistical significance. The immunohistochemical staining showed the expression of HSP90 in the experiment group （10/12, 83.3 %） was significantly lower than that in the control group （4/12, 33.3 %） （P%0.05）, and the expression of VEGF in the experiment group （10/12,83.3%） was significantly lower than that in the control group （4/12, 33.3%） （P〈0.05）. The similar expressions could also be detected in the western blotting （P〈0.01）. Conclusions 17-AAG has a significant effect on the transplanted rat pheochromocytoma in nude mice and suppresses the expression of HSP90 and VEGF in the tumor tissues.

关 键 词：嗜铬细胞瘤 血管内皮生长因子 热休克蛋白90 17-丙稀胺-17-去甲氧格尔德雷素 

分 类 号：R737.1[医药卫生—肿瘤]