肝癌细胞中GnRH受体的作用机制及其信号转导途径

Recent studies have shown that many neuropeptides and gastrointestinal hormone can regulate the growth of some kinds of tumors, As an effective treatment regimen for tumor management, endocrine therapy has caused much attention by tumor pathologists and clinicians. The present study investigated the mechanism of action of gonadotropin-releasing hormone(GnRH) receptor on hepatoma cell and its signal transduction by using morphologic and modern molecular biology techniques. The following innovating results have been obtained: human hepatoma tissue and cell have the function of GnRH autocrine; GnRH analogues can inhibit the hepatocarcinoma cell proliferation and induce cell apoptosis; many signal molecules(such as Ca2+, PIK, PKC etc.) are involved in the activtes of hepatocarcinoma cell apoptosis induced by GnRH. With immunohistochemical method, we determined the relationship between the changes GnRH receptor gene expression and Fas/FasL system, TNF(tumor necrosis factor), and P53, the results showed that the up-regulate of GnRH receptor expression was associated with TNF-α and Bax proteins increased in hepatocarcinoma tissues, suggesting that the GnRH receptor expression is related to the cancer cell apoptosis in human hepatocarcinoma tissues. GnRH analogues can increase the of Fas/FasL gene expression in hHCC and SMMC-7721 hepatoma cell by semi-quantitative RT-PCR technique,, suggesting that GnRH analogues can induce human hepatoma cell apoptosis This study have important theoretical significance and clinical value in understanding the pathogenesis of heaotocarcinoma and its endocrine therapy.

采用形态学和分子生物学研究方法，检测人肝癌细胞GnRH受体对GnRH类似物治疗的反应；并观察GnRH-R基因表达变化与FasL/fas系统、TNF、Bax及P53的关系，以阐明肝癌细胞中GnRH-R的作用机制。从信号转导早期信号分子（TPK/PTP和PIK）、第二信使（Ca2+、IP和cAMP）托вΨ肿樱≒KC、PKA、Ras和Ap1）三个环节探讨GnRH-R介导的肝癌细胞增殖信号转导途径Ｎ狦nRH治疗肝癌提供依据。