生长激素荷人结肠癌裸鼠GH/IGF-I/IGFBP-3轴的影响  

Impact of exogenous growth hormone on GH/IGF/IGFBP axis in colon cancer-bearing nude mice

作　　者：张毅[1] 梁道明[1] 李思齐[1] 袁勇[1] 赵辉[1] 陈嘉勇[1] 

机构地区：[1]昆明医科大学第二附属医院急诊科,云南昆明650101

出　　处：《中国普通外科杂志》2013年第4期442-446,共5页China Journal of General Surgery

基　　金：国家自然科学基金资助项目(30460133)

摘　　要：目的:探讨外源性生长激素(GH)对荷瘤裸鼠GH/胰岛素样生长因子(IGF)/胰岛素样生长因子结合蛋白3(IGFBP-3)轴的影响。方法:采用人结肠癌细胞株(HCT116)建立人结肠癌细胞裸鼠移植瘤模型。取48只荷瘤裸鼠随机均分为生理盐水处理组(NS组)、氟尿嘧啶处理组(FU组)、GH处理组(GH组),FU+GH处理组(FU+GH组)。每组连续给药6 d,在给药结束后24,72 h分别处死每组6只动物,取血及移植瘤标本,应用ELISA法检测血清GH,IGF-I,IGFBP-3含量和RT-PCR法检测移植瘤IGF-I,IGF-I受体(IGF-IR),IGFBP-3的mRNA表达。结果:ELISA结果显示,给药结束后24 h,GH组和FU+GH组血清GH,IGF-I,IGFBP-3含量较NS组与FU组明显升高(均P<0.05);给药结束后72 h,各组GH,IGF-I的水平无统计学差异(均P>0.05),但GH组和FU+GH组IGFBP-3水平仍高于NS组和FU组(均P<0.05)。RT-PCR结果显示,给药结束后24 h,GH,FU,FU+GH组移植瘤组织IGF-I mRNA与IGF-IR mRNA的表达较NS组明显降低,而IGFBP-3 mRNA表达明显增加;给药结束后72 h,IGF-I mRNA与IGF-IR mRNA表达各组间无差别,但GH组,FU组和FU+GH组IGFBP-3 mRNA表达量仍明显高于NS组。结论:短期应用外源性GH所致GH/IGF/IGFBP-3轴的变化对人结肠癌移植瘤生长无促进作用。Objective： To observe the impact of exogenous growth hormone （GH） on the axis of GH/insulin-like growth factor I （IGF-I）/insulin-like growth factor binding protein （GFBP） in colon cancer-bearing nude mice. Methods： Nude mice xenograft models of human colon cancer were established by using human colon cancer HCT 116 cells. Subsequently, 48 tumor-bearing mice were equally randomized into normal saline treatment group （NS group）, fluorouracil treatment group （FU group）, GH treatment group （GH group） and FU plus GH treatment group （FU＋GH group）, and all treatment regimens were continued for 6 days. Mice were sacrificed to collect the blood and tumor xenograft samples at 24 and 72 h after the termination of regimens with 6 mice in each group. The serum contents of GH, IGF-I and IGFBP-3 were determined by ELISA assa）5 and the mRNA expressions of IGF-I, IGF-I receptor （IGF-IR） and IGFBP-3 in xenograft were detect by RT-PCR method. Results： The results of ELISA showed that the serum levels of GH, IGF-I and IGFBP-3 were significantly increased in GH group and FU＋GH group compared with either NS group or FU group at 24 h after regimen discontinuation （all P〈0.05）; at 72 h after regimen discontinuation, the serum levels of GH and IGF-I were similar among groups （both P〉0.05）, but the IGFBP-3 levels in GH group and FU＋GH group were still higher than that in NS group or FU group （all P〈0.05）. The results of RT-PCR showed that the mRNA expressions of IGF-I and IGF-IR were obviously decreased but IGFBP-3 mRNA expression was markedly increased in tumor xenografts in either GH group or FU group or FU＋GH group compared with NS group at 24 h after regimen discontinuation; at 72 h after regimen discontinuation, both IGF-I and IGF-IR mRNA expressions were similar among groups, but IGFBP-3 mRNA expressions in above three groups were still higher than that in NS group. Conclusion： The alteration in GH/IGF/IGFBP axis resulting from short-term exogenous GH application ex

关 键 词：结肠肿瘤 人生长激素 异种移植模型抗肿瘤试验 小鼠 裸 

分 类 号：R735.35[医药卫生—肿瘤]