| Hepatocellular carcinoma(HCC) is a high malignant tumor with high incidence in our country. And at present HCC is still a dangerous life threatening disease of mankind. In various treatment strategies of HCC, surgical resection of tumor body is still the best choice. Nevertheless, because most patients were advanced liver cancer when they were admitted to hospital for diagnosis, they lost the chances for operation. As for conservative management, chemotherapy and radiotherapy have limited efficacy for inoperable HCC with serious side effects. So much effort have been made to search for a new treatment method for HCC with high efficacy and nontoxicity. Recently endocrine therapy(or called hormone therapy), as an effective treatment regimen for tumor management has caused much attention by many tumor pathologist and clinicians. Gonadotropin-releasing hormone (GnRH) is a decapeptide synthesized by hypothalamus and released from nerve terminals in pulsatile manner into the hypophysial-portal circulation and stimulates gonadotropin target cells in anterior pituitary. The gonadotropin response to GnRH stimulation is manifested by releasing the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH) that play a central role in control of reproduction. Recently, GnRH and its receptor have been found existin many extra-hypothalamus and extra-pituitary tissuses, such as immune system ( T and B lymphocytes ),and gonad (ovary, oviduct, prostate, testis, placenta, et al). They are not only expressed in normal tissues, but also widely exist in various carcinoma that derived from reproductive (ovary cancer, prostate cancer) or non-reproductive tissues (breast cancer, lung cancer, pancreas cancer and hepatocellular carcinoma, et al). These indicate that they may have certain functions in regulating the growth of these neoplastic tissues.Both experimental and clinical evidence have suggested that liver cancer might be a hormone-dependent neoplasia. A more recent study has shown that the human HCC-derived cell lines contain gonadotropin-releasing hormone receptors(GnRH-R) and respond to natural GnRH in term of suppressed proliferation in vitro. To explore the possible relationship between GnRH and its receptor and some biological characteristic of HCC, we conducted the following experiments:[1] By using immunohistochemistry and in situ hybridization, we detected the expression of GnRH and its receptor in human cultured hepatocellular carcinoma(HCC) cell line SMMC-7721 in vitro. [2] MTT assay, agarose gel electrophoresis, transmission electron microscopy and DNA end labeling method were used to detected effects of GnRH analogue on the proliferation of human cultured hepatocellular carcinoma cell which have been treated by GnRH analogue alarelin.[3] In order to study the possible mechanism of GnRH receptor mediated intraellular message transduction in cultured human hepatocellular carcinoma cell, Radioimmuoassay was used to study the effects of GnRH analogue on PKC activity in cultured human hepatocellular carcinoma cell . The main results were as follows:1. By using immunohistochemistry and in situ hybridization, human cultured hepatocellular carcinoma cells showed Both GnRH and its receptor immunoreactivity , positive staining was located in cytoplasm rather than in nuclei, GnRH receptor was the products of the hepatocellular carcinoma cells and the hepatocellular carcinoma cells also are targets of GnRH, These results suggested that hepatocellular carcinoma cells can synthesize and secrete GnRH; GnRH might be involved in the regulation of hepatocellular carcinoma cells functions by autocrine mechanism.2. SMMC-7721 cell was induced by alarelin in 10-9mol/L concentration. The induction of apoptosis was dose - effect dependent. Under electron microscopy we could identify the earlier and later stage of apoptosis cells,and chromatin condensation, as well as apoptosis body formation could be observed. DNA end labeling method identified that alarelin could induced apoptosis of...
|
PDF Full Text Request