PP242对大鼠嗜铬细胞瘤裸鼠移植瘤的抑制作用  

Inhibitory effect of PP242 on transplanted rat pheochromocytoma in nude mice

作　　者：赵跃广 余志贤[2] 朱军华 吕海鸥 张小华[3] 

机构地区：[1]永康市第一人民医院泌尿外科,浙江永康321300 [2]温州医科大学附属第一医院泌尿外科,浙江温州325000 [3]上海交通大学医学院附属瑞金医院泌尿外科,上海200025

出　　处：《实用肿瘤杂志》2015年第6期516-520,共5页Journal of Practical Oncology

摘　　要：目的探讨哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,m TOR)双靶向抑制剂PP242对大鼠嗜铬细胞瘤裸鼠移植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,裸鼠成瘤后随机分为3组,每组10只,分别为PP242组(PP242灌胃10 mg/kg,1天1次)、雷帕霉素组(雷帕霉素灌胃1 mg/kg,1天1次)和对照组(生理盐水灌胃10 m L/kg,1天1次),用药2周,期间测量裸鼠移植瘤的体积变化。给药结束后,切取肿瘤组织采用TUNEL法检测肿瘤组织凋亡情况,Western blot检测肿瘤组织中VEGF的表达。结果给药结束后,PP242组的移植瘤体积为(893.01±31.22)mm3,雷帕霉素组为(1 519.01±32.61)mm3,对照组为(2 341.98±23.07)mm3,3组间差异有统计学意义(P<0.05)。TUNEL结果表明,PP242组的肿瘤组织细胞凋亡率高于雷帕霉素组,雷帕霉素组细胞凋亡率高于对照组(均P<0.05)。Western blot结果表明,PP242组肿瘤组织的VEGF表达低于雷帕霉素组,而雷帕霉素组低于对照组(P<0.05)。结论 m TORC1/C2复合体双靶向抑制剂PP242对大鼠嗜铬细胞瘤裸鼠移植瘤有明显抑制作用,并可有效降低肿瘤组织中VEGF的表达,其作用强于m TORC1抑制剂雷帕霉素。： Objective To investigate the effect of mammalian target of rapamycin （mTOR） inhibitor PP242 on rat pheochromocytoma. Methods Rat pheochromocytoma PC12 cells were inoculated subcutaneously into 30 nude mice to establish transplanted tumor model. The animals were randomly divided into 3 groups with 10 in each group： PP242 group received oral administration of PP242 （ 10 mg/kg）, rapamycin group received rapamycin （ 1 mg/kg） and control group received normal saline, respectively. The volume of tumor was measured during the period of experiments. After 2 weeks of drug administration the mice were sacrificed and tumor tissues were harvested. Cell apoptosis was detected by TUNEL and the expression of VEGF in tumor tissue was detected by Western blot. Results The average volume of tumor was （ 893.01 ±31.22） mm^3 in PP242 group, （ 1 519.01 ±32.61 ） mm^3 in rapamycin group and （2 341.98 ±23.07） mm^3 in control group. PP242 significantly inhibited the tumor growth in nude mice （P 〈 0.05 ）. The apoptosis rate in tumor treated with PP242 was significantly higher than that in group treated with rapamycin （ P 〈 0.05 ）. Compared with other two groups, the expression level of VEGF was significantly decreased in tumor treated with PP242 （P 〈 0.05）. Conclusion PP242 can inhibit the growth and enhance the cell apoptosis of transplanted rat pheochromocytoma in nude mice with down-regulated expression of VEGF in tumor tissue.

关 键 词：嗜铬细胞瘤/药物疗法 PC12细胞 信号传导 西罗莫司/拮抗剂和抑制剂 蛋白激酶类 哺乳动物 

分 类 号：R736.6[医药卫生—肿瘤]