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目的:研究重组人生长激素(recombinant hunman growth hormone,rhGH)对裸鼠肝癌移植瘤生长和转移能力的影响及相关信号转导通路的变化。方法:通过RNA干扰技术抑制MHCC-97H肝癌细胞中胰岛素样生长因子-1受体(insulin-like growth factor-1 receptor,IGF-1R)的表达。建立裸鼠皮下和原位肝癌移植模型;研究IGF-1R基因沉默前后,rhGH对裸鼠肝癌移植瘤成瘤、生长和转移的影响,并用Western印迹法检测PI-3K信号转导通路中,信号分子AKT的蛋白表达和磷酸化水平。结果:注射rhGH可使荷瘤裸鼠体重明显增加,肝癌原位移植瘤体积显著增大(P<0.05);但肝癌在裸鼠体内的转移并未显著增加(P>0.05)。IGF-1R基因沉默后,裸鼠皮下移植瘤的成瘤率、原位肝癌接种模型中的肝癌移植瘤体积均显著减小(P<0.05)。同时,注射rhGH后,裸鼠肝癌移植瘤体积无明显增大(P>0.05)。对PI-3K信号通路的研究显示,rhGH能显著促进MHCC-97H肝癌细胞信号分子AKT磷酸化,IGF-1R沉默后AKT磷酸化水平明显降低(P<0.05)。结论:rhGH在体内具有显著促进荷瘤裸鼠体重增加及移植瘤生长的作用;但并不促进肝癌的转移。IGF-1R基因沉默后,rhGH对裸鼠移植瘤的成瘤和促生长作用明显减弱。而PI-3K信号通路在rhGH促肝癌生长中发挥重要的介导作用。
Objective: To study the effects of recombinant human growth hormone (rhGH) on the growth and metastasis of hepatocellular carcinoma in nude mice and the related signal transduction pathways. Methods: The RNA interference technique was used to inhibit the expression of insulin-like growth factor-1 receptor (IGF-1R) in MHCC-97H hepatoma cells. To study the effect of rhGH on tumorigenesis, growth and metastasis of hepatocellular carcinoma xenografts in nude mice before and after IGF-1R gene silencing. The signal transduction pathway of PI-3K was detected by Western blotting. Molecular AKT protein expression and phosphorylation levels. Results: The body weight of nude mice injected with rhGH increased significantly, and the volume of orthotopic transplanted hepatocellular carcinoma increased significantly (P <0.05). However, the metastasis of hepatocellular carcinoma in nude mice did not increase significantly (P> 0.05). After the IGF-1R gene was silenced, the tumor-bearing rate of subcutaneous xenografts in nude mice and the volume of hepatocellular carcinoma xenografts in in situ hepatocellular carcinoma inoculation model were significantly reduced (P <0.05). At the same time, the volume of transplanted hepatoma in nude mice did not increase significantly after rhGH injection (P> 0.05). The study of PI-3K signaling pathway showed that rhGH can significantly promote the AKT phosphorylation of MHCC-97H hepatocellular carcinoma cells, and AKT phosphorylation was significantly decreased after IGF-1R silencing (P <0.05). Conclusion: rhGH can significantly increase the body weight of tumor-bearing nude mice and the growth of transplanted tumor in vivo, but it does not promote the metastasis of liver cancer. After IGF-1R gene silencing, the effect of rhGH on the tumorigenesis and growth-promoting effect of transplanted xenografts in nude mice was significantly weakened. The PI-3K signaling pathway in rhGH promote liver cancer play an important mediator.