摘要：目的 运用小分子干扰GHR(siGHR)技术获取生长激素受体（GHR）基因差异表达的人胃癌MGC803细胞株，探讨rhGH干预GHR不同表达状态细胞株植入裸鼠体内的移植瘤生长情况及JAK2/STAT3通路关键节点基因表达变化。方法 Western-Blot法鉴定亲本及转染后细胞株GHR表达状态，72只接种皮下移植瘤的裸鼠随机分为：对照组(生理盐水0.2ml/d)，低剂量rhGH组(1U/(kg·d))和高剂量rhGH组(3U/(kg·d))，连续给药21d，观察并记录裸鼠体质量和肿瘤体积，免疫组织化学法检测胃癌组织中VEGF蛋白表达，Western- Blot法测JAK2-STAT3通路节点蛋白变化。结果 转染空载体细胞株GHR蛋白表达量与亲本细胞株差异不明显（P>0.05），转染干扰载体株较亲本细胞株GHR蛋白下降57%。对于接种亲本及空载质粒转染的人胃癌细胞株MGC803的裸鼠，rhGH给药组皮下移植瘤体积较对照组增大(P<0.05)，且rhGH组促增长效应显著(P<0.05)，3组间体重差异不明显(P>0.05)；VEGF蛋白表达较对照组升高，JAK2、STAT3、p-JAK2、p-STAT3含量增加；对于GHR表达下调的人胃癌细胞株MGC803的裸鼠，给药组体重大于对照组(P<0.05)，而3组之间肿瘤体积大小、VEGF蛋白表达水平及JAK2/STAT3通路重要节点蛋白含量比较差异均无统计学意义(P>0.05)。结论 rhGH能促进GHR阳性表达的MGC803移植瘤生长，但对经siGHR技术抑制GHR基因表达的MGC803移植瘤未表现出促肿瘤生长效应，其机制可能与血清VEGF分泌及JAK2-STAT3信号转导通路节点基因功效有关。

Abstract: Objective To knock down growth hormone receptor(GHR) in MGC-803 cells using vector-based small interference GHR (siGHR), and thereby to investigate the effects of recombinant human growth hormone(rhGH) on tumor growth and JAK2/STAT3 pathway of human gastric carcinoma xenografts with different expression states of GHR in nude mice. Methods Seventy-two male nude mice were bought for the experiment. Western-blotting method was used to detect the expressions of growth hormone receptor(GHR) in parental and transfected human gastric carcinoma cell lines MGC803. The gastric carcinoma cell lines of different GHR expression were then injected subcutaneously into 72 nude mice to create the subcutaneous xenografts models. These models were then randomly divided into three experimental groups: the control group(0.9%NaCl,0.2ml/d), the low-dose rhGH group(1U/(kg·d), 0.2ml/d) and the high-dose rhGH group(3U/(kg·d), 0.2ml/d). The mice in each group were all treated with different doses of drugs for 21 days continuously. The changes of body weights and tumor volumes of nude mice in each group were recorded. VEGF protein expressions in tumor tissues were detected by immunohistochemical method. Western Blot was performed to detect the components of JAK2/STAT3 signaling pathway. Results There is no significance of GHR expression in protein level between MGC-803 and MGC803-NC pGPU6/GFP/Neo-scramble-transfected cells(replaced with)(P>0.05). Compared to MGC-803 the GHR expression in pGPU6/GFP/Neo-shGHR-transfected cells(replaced with MGC803-shGHR) decreased significantly(protein decreased 57%). For parental and MGC803-NC groups, after giving rhGH for 21 days, the tumor volumes were significantly larger in the 3.0U/(kg·d) rhGH group than in the 1.0U/(kg·d) rhGH group and the control group(P<0.05). No significant difference was found in body weights of the nude mice among these 3 groups(P>0.05). Moderate positive staining with VEGF was observed in thecontrol group, while VEGF staining was strongly seen in rhGH administration groups. The expressions of p-JAK2 and p-STAT3 proteins for the 3.0U/(kg·d) rhGH group were both significantly higher than the 1.0U/(kg·d) rhGH group and the control group. The total JAK2 and STAT3 expressions of the 3 groups did not differ significantly(P>0.05). While for MGC803-shGHR groups, the body weights of the nude mice of 3.0U/(kg·d) rhGH group were much heavier than the 1.0U/(kg·d) rhGH group and the control group, but no obvious increasing effects on tumor growth and the expressions of VEGF, p-JAK2 and p-STAT3 were observed(P>0.05).Conclusions Recombinant human growth hormone can promote the growth of tumor in the MGC-803 and MGC803-NC xenograft tumor models in which GHR is highly expressed, but not for the MGC803-shGHR xenograft tumor models in which the expression of GHR is deeply decreased. Down-regulation of components of the expression of VEGF and JAK2/STAT3 signaling pathway may be the potential mechanisms.