重组人生长激素对裸鼠肝癌移植瘤生长转移的实验研究

Studies on effects of human recombinant growth hormone on xenograft hepatocellular carcinoma in nude mice

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 investigate the effects of rhGH on growth and metastasis of xenograft transplantation of hepatocellular carcinoma in nude mice and to explore the underlying mechanism.Methods MHCC97-H hepatocellular carcinoma cells,with or without IGF-1R silencing,were planted in nude mice to observe the effects of transplantable tumor formation,growth and metastasis.The expression and phosphorylation of signal transduction molecules AKT were detected by Western-blotting.Results The nude mice injected with rhGH were heavier than the controls and the volumes of transplantable tumor were bigger,but the numbers of liver and pulmonary and lymph node micrometastatis in the rhGH group were not significantly higher when compared with the control group.rhGH did increase the phosphorylation of ATK significantly,but the above parameters went to the opposite direction when the silencing effect of the IGF-1R gene offsetted that of the rhGH on hepatocellular carcinoma cells.Conclusions rhGH can increase the weight of hepatocellular carcinoma cell in the nude mice and stimulate the growth of transplantable tumors,but do not have significant impact on the invasion and metastastic capacity of the hepatocellular carcinoma.IGF-1R and the underlying signal transduction pathway PI-3K/AKT play key roles in offsetting the effects of rhGH.