重组人生长激素对人肝癌细胞Bel-7402裸小鼠移植瘤生长的影响

背景与目的:在原发性肝癌患者围手术期应用重组人生长激素(recombinanthumangrowthhormone,rhGH),于改善患者状况同时是否会促进原有肿瘤生长、转移与复发,鲜见相关的研究报道。大多数原发性肝癌能表达生长激素受体(growthhormonereceptor,GHR),本研究拟探讨rhGH对表达GHR的人肝癌细胞Bel-7402裸小鼠移植瘤生长的影响。方法:放射配体分析法证实肝癌细胞Bel-7402表达GHR后行裸鼠肝内移植,将32只肝内移植人肝癌细胞Bel-7402的裸小鼠随机分为4组:1组为对照组,实验组则根据rhGH剂量不同分为3组[即0.5u·(kg·d)-1、1.0u·(kg·d)-1、2.0u·(kg·d)-1]。在肝脏肿瘤移植术后2周开始动物皮下注射rhGH2周,实验结束处死动物,检查肿瘤情况;用抗增殖细胞核抗原(proliferationcellnuclearantigen,PCNA)单克隆抗体免疫组化染色检测瘤组织PCNA表达情况。结果:移植瘤组织的重量与体积在rhGH1.0u·(kg·d)-1、2.0u·(kg·d)-1组与对照组之间比较有显著性差异(P<0.05),但0.5u·(kg·d)-1组与对照组无显著性差异(P>0.05)。各实验组肿瘤PCNA标记指数(labelingindex,LI)均高于对照组(P<0.05),各实验组之间相互比较差异亦有统计学意义(P<0.05)。rhGH用药剂量与LI显著相关(r=0.779,P<0.001)。结论:rhGH能促进裸小鼠肝脏人肝癌细胞Bel-7402移植瘤的生长,其作用有随用药量增加而增强的趋势,两者之间存在一定相关性。

Effect of recombinant human growth hormone on growth of human Bel-7402 hepatic carcinoma xenografts in nude mice

BACKGROUND & OBJECTIVE: Recombinant human growth hormone (rhGH) has been widely used in clinical medicine; while for the patients with hepatocellular carcinoma (HCC), if rhGH could cause tumor growth, metastasis or recurrence other than improve patients' body condition is uncertain. Because most primary hepatic carcinoma could express human growth hormone receptor (GHR), this study was to explore the effects of rhGH on the growth of human Bel-7402 hepatic carcinoma (with GHR expression) xenograft in nude mice. METHODS: The expression of GHR was confirmed in Bel-7402 cells by radioligand assay. After transplantation of Bel-7402 hepatic carcinoma in liver, 32 nude mice were randomly divided into 4 groups. Except 1 control group, 3 experimental groups were injected with different dosages of rhGH [0.5, 1.0, and 2.0 U . (kg.day)(-1), respectively] subcutaneously 2 weeks after tumor transplantation, once a day for 2 weeks. All nude mice were killed at the end of the experiment to observe the growth of xenografts. The expression of proliferating cell nuclear antigen (PCNA) in xenografts was examined by immunochemistry. RESULTS: The tumor weight was significantly heavier and the tumor volume was significantly larger in 1.0 U . (kg.day)(-1) rhGH and 2.0 U . (kg.day)(-1) rhGH groups than in control group (P<0.05), but no significant difference was found between 0.5 U . (kg.day)(-1) rhGH group and control group (P>0.05). Labeling index (LI) of PCNA was significantly higher in each experimental group than in control group (P<0.05), and significant differences were also found among the 3 experimental groups (P<0.05). The dosage of rhGH was positively correlated to LI of PCNA in tumor tissues (r=0.779, P<0.001). CONCLUSIONS: rhGH could enhance the growth of Bel-7402 hepatic carcinoma xenografts in nude mice. Its effect positively correlates with rhGH dosage.