抑制EGF-1受体表达对人鼻咽癌裸鼠移植瘤生物学行为的影响  

Effect of IGF-1 Receptor Expression Inhibition on Human Laryngeal Xenografts Carcinoma in Nude Mice

作　　者：吴红年[1] 袁玉林[2] 周绪红[3] 

机构地区：[1]咸宁学院医学院人体解剖学教研室,湖北咸宁437100 [2]武汉大学医学院人体解剖学与组织胚胎学系 [3]武汉大学中南医院耳鼻喉科,湖北武汉430071

出　　处：《解剖科学进展》2009年第1期80-84,共5页Progress of Anatomical Sciences

摘　　要：目的诱导IGF-I受体基因沉默的shRNA真核表达质粒的在体抗瘤效应,探讨RNA干扰IGF-I受体基因对裸鼠人鼻咽癌移植瘤的生物学行为的影响。方法将右侧背部接种人鼻咽癌CNE2细胞后,肿瘤直径达5～7mm的24只裸鼠随机分为3组:A组为IGF-1RmRNA特异性真核表达质粒(pshRNA1)治疗组,瘤体内多点注射pshRNA1;B组为pshRNA2质粒载体对照组,瘤体内多点注射阴性质粒载体pshRNA2(剂量同A组);C组为生理盐水对照组,瘤体内多点注射0.3ml生理盐水。从开始治疗后3周处死裸鼠,分离肿瘤,部分做共聚焦观察质粒转染情况,其余肿瘤组织观察肿瘤组织的病理变化和IGF-I受体蛋白在瘤体内的表达变化。结果所有裸鼠移植瘤接种成功,14d左右肿瘤直径达5～7mm。治疗裸鼠7d后,pshRNA1治疗组抑制率达67.21%,瘤体积明显小于阴性质粒组和生理盐水组(P<0.05),阴性质粒组与对照组无显著差异。pshRNA1治疗组移植瘤可见大片癌组织表达绿色荧光,其中仅少数细胞为IGF-IR阳性细胞。阴性质粒组癌组织也表达绿色荧光,但IGF-IR阳性细胞数明显多于pshRNA1治疗组(p<0.05),而生理盐水组的移植瘤未见绿色荧光。结论shRNA干扰IGF-I受体基因能在体内有效下调IGF-I受体蛋白的表达、抑制鼻咽癌裸鼠移植瘤的生长。Objective To explore the effect of interfering insulin like growth factor-1 receptou （IGF-IR） mRNA by shRNA expression vectors on nasopharyngeal carcinoma xenograft in nude mice. Methods Short hairpin RNA expression vectors targeting the mRNA of IGF-IR （pshRNA1） and control pEGFP without additional sequence（pshRNA2） were constructed and transfected into the subcutaneous xenograft tumors in the nude mice. Fluorescence expression in the tumor was detected by laser confocal microscopy. Tumor morphology was observed with HE staining and the expression of IGF-IR in tumor was determined by SP method. Results Human nasopharyngeal carci＇moma was xenografted successfully in all nude mice, the diameter of the tumor reached 5 - 7mm 14 days after xenogra：ft. Many green fluorescent cells were observed in pshRNA1 group, among which less positive IGF-IR cells were observed .The fluorescent cells were also observed in pshRNA2 group with more number of positive IGF-IR cells. The tumor volume was significantly smaller in pshRNA1 compared with the saline group and pshRNA2 group, and also the inhibitory rate of tumor cells was 67.21% seven days after injection of pshRNA1 . Conclusion Short hairpin RNA plasmid directed against IGF-IR mRNA could downregulate the expression of IGF-IR and inhibit the nasopharyngeal carcinoma in nude mice.

关 键 词：EGF-1受体 鼻咽癌 SHRNA 

分 类 号：R739.6[医药卫生—肿瘤]