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| Different Growth Hormone Receptor Expression in Human Gastric Carcinoma and the Proliferative Effects of Recombinant Human Growth Hormone |
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Abstract 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.
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2014, Vol. 1 
