重组人生长激素对裸鼠人胃癌移植瘤组织生长及Janus激酶2-信号转导与转录激活因子3通路的影响  

Effects of recombinant human growth hormone on tumor growth and access relevant to Janus kinase 2-sig. nal transducer and activator of transcription 3 of human gastric carcinoma xenografts in nude mice

作　　者：权明[1] 曹鹏[2] 李苏宜 

机构地区：[1]东南大学附属中大医院肿瘤科,南京210009 [2]江苏省中医药研究院分子生物学实验室,南京210028

出　　处：《中华临床营养杂志》2011年第3期171-177,共7页Chinese Journal of Clinical Nutrition

摘　　要：目的探讨重组人生长激素（rhGH）对荷人胃癌裸鼠移植瘤生长及Janus激酶2-信号转导与转录激活因子3通路相关的肿瘤血管生成因子的影响。方法采用免疫细胞化学染色法筛选出生长激素受体阳性（GHR^＋）和阴性（GHR^-）细胞株各1株，分别接种于裸鼠皮下，建立GHR不同表达状态胃癌裸鼠皮下移植瘤模型，将裸鼠随机分为对照组、低剂量rhGH组和高剂量rhGH组，连续给药14d，观察并记录裸鼠体重及肿瘤体积的变化，RT-PCR、Western-bolt检测肿瘤血管生成因子mRNA及蛋白表达。结果SGC-7901细胞株GHR强阳性表达，MKN-45不表达GHR。SGC-7901接种裸鼠，低剂量rhGH组和高剂量rhGH组肿瘤体积[（1．141±0．234）和（2．106±0．260）cm^3]较对照组[（0．6124±0．156）cm^3]增大（P=0．034，P=0．001），高剂量rhGH促增长效应最为显著（P=0．043），各组间裸鼠体重差异无统计学意义；低剂量rhGH可促SGC-7901血管生成因子mRNA表达，GHR、Janus激酶2、信号转导与转录激活因子3、血管内皮生长因子（VEGF）、缺氧诱导因子1et（HIF-1α）、成纤维细胞生长因子和基质金属蛋白酶2（MMP-2）的P值分别为：0．001、0．011、0．042、0．045、0．040、0．002和0．003，但高剂量组未增加；低剂量rhGH组血管生成因子的蛋白表达水平明显升高，。磷酸化信号转导与转录激活因子3、信号转导与转录激活因子3、VEGF、HIF-lα和MMP-2的P值分别为：0．015、0．003、0，010．0，008和0．005，高剂量组VEGF、HIF-lα和MMP-2较低剂量组表达增加（P=0．012，P=0．025，P=0．046）。MKN-45接种裸鼠，低剂量rhGH组和高剂量rhGH组裸鼠体重[（24．94±0．517）和（26．97±0．686）g]较对照组[（22．78±0．418）g]增加（P=0．040，P=0．012），肿瘤体积、血管生成因子mRNA及蛋白水平各组之间差异无统计学意义。结论rhGH促GHR^＋的SGC-7901移植瘤生长，并促肿瘤�Objective To investigate the effects of recombinant human growth hormone （rhGH） on tumor growth and tumor angiogenesis factor relevant to Janus kinase 2-signal transducer and activator of transcription 3 of human gastric carcinoma xenografts in nude mice with different expressions of growth hormone receptor （GHR）. Methods Immunocytochemical method was used to pick out one GHR-positiveland one GHR-negative cell line. The cells were subcutaneously injected into 26 nude mice separately, then the patterns of xenografts in nude mice with different expressions of GHR were established. The nude mice bearing two different kinds of humangastric caicinoma were equally randomized into control group, low-dose rhGH group, and high-dose rhGH group, and were treated with drugs for 14 days. Changes of tumor volumes and body weight of nude mice were record. The protein and mRNA expressions of tumor angiogenesis factor in tumor tissue were detected by RT-PCR and Western blot, respectively. Results GHR was highly expressed in SGC-7901 cells but negative in MKN-45 cells. For nude mice bearing GHR^＋SGC-7901 xenografts, the tumor volumes were significantly larger in low-dose rhGH group [ （ 1. 141 ±0. 234） cm3 ] and high-dose rhGH group [ （2. 106 ± 0. 260） cm^3 ] than in control group [ （0. 612 ± 0. 156 ） e m3 ] （P = 0. 034, P = 0. 001 ）, and the high-dose rhGH group revealed greater effect （P = 0. 043）. Body weight was not significantly different among three groups. Compared with the control group, the mRNA expressions of tumor angiogenesis factor were significantly increased in low-does rhGH group, and the P values of GHR, Janus kinase 2, signal transducer and activator of transcription 3, vascular endothelial growth factor （VEGF）, hypoxia-indueible factor-let （HIF-lct）, fibroblast growth factor, and matrix metalloproteinases-2 （MMP-2） was 0. 001, 0. 011, 0. 042, 0. 045, 0. 040, 0. 002, and 0. 003, respectively; however, the highdoes rhGH group did not show the greater effects. The protein

关 键 词：重组人生长激素 生长激素受体 胃癌 肿瘤血管生成因子 

分 类 号：R735.2[医药卫生—肿瘤]