原发性肝癌组织中生长激素受体的表达及其意义

Expression of Growth Hormone Receptor in Hepatocellular Carcinomaand Its Significance

背景与目的:重组人生长激素(recombinehumangrowthhormone,rhGH)在调节代谢、降低外科病人死亡率方面,疗效明显,然而rhGH能否用于治疗原发性肝癌患者,目前存在较大争议。由于生长激素必须通过与其受体(growthhormonereceptor,GHR)结合方能发挥作用,因此本研究旨在通过了解原发性肝癌(hepatocellularcarcinoma,HCC)组织生长激素受体的表达情况,探讨rhGH在肝癌患者中是否适用。方法:应用放射性配体法对40例HCC组织进行GHR的检测,以6例正常肝组织作为对照,肝组织GHR的受体最大结合量(RT)和平衡解离常数(Kd)采用Scatchard法计算;并分析肝癌GHR的RT值与肝癌临床病理特点之间的关系。结果:在正常肝组织与35例HCC组织中检测到单一的生长激素(GH)特异性结合位点(即GHR),对照组肝组织GHR的RT值为(39.5467±3.4770)fmol/mgprotein,Kd为(0.6167±0.1007)nmol/L,肝癌组织GHR的RT为(18.5416±4.1686)fmol/mgprotein,肝癌组织GHR的Kd值为(0.6319±0.1978)nmol/L,与正常肝组织相比,肝癌GHR的RT显著性降低(P<0.05),而Kd无显著性改变(P>0.05);肝癌组织GHR的RT值与肿瘤大小、患者临床分期呈显著性负相关,而与肿瘤分化程度、患者年龄、是否合并肝硬变无显著性相关。在5例肝癌组织未检测到GHR。结论:本组结果显示。

BACKGROUND &OBJECTIVE: Recombinant human growth hormone (rhGH) has been proved effective in clinic, such as promoting protein synthesis and decreasing the mortality. But there are still many arguments on whether it can be used in hepatocellular carcinoma (HCC) patients. rhGH cannot work except that it combines to its own receptor growth hormone receptor (GHR). The current study was designed to explore the expression of GHR in HCC tissues and to investigate the viability of rhGH for HCC treatment. METHODS: Radioreceptor assays were used to determine growth hormone receptor (GHR) in 40 HCC tissues; 6 normal liver tissues were used as control. Receptor binding capacity(RT) and affinity constant(Kd) of GHR were calculated by Scatchards method; the relationship between RT of GHR in cancer and clinicopathologic factors were also analyzed. RESULTS:The growth hormone specific singular binding site, namely GHR, was detected respectively in 35 HCC cases and control tissues. The RT and Kd of GHR were 18.5416±4.1686 fmol/mg protein and 0.6319±0.1978 nmol/L in tumor tissues, 39.5467±3.4770 fmol/mg protein and 0.6167±0.1007 nmol/L in control tissues, respectively. Compared with the normal liver tissue, RT of GHR in tumor was lower (P< 0.05) but Kd did not show any difference(P >0.05).The RT of the GHR was negatively relevant to the tumor size and disease stage, but was not associated with differentiation of tumor, ages of the patients or whether the patient suffered from cirrhosis at the same time. GHR was undetectable in 5 cases. CONCLUSION: This study showed that most of the HCC tissues express low levels of GHR. Before their functions are well understood, rhGH should be very carefully used in HCC patients.