The Somatostatin Receptor â…¡ And The Specific Agonist In The Colorectal Cancer

BackgoundColorectal cancer is an important cause of cancer death worldwide. The therapy outcome of the colorectal cancer is not satisfactory yet despite the efforts on various therapeutic modalities during passed years. To improve the therapy outcome of colorectal cancer, lots of research work is going on in different ways. It shows that some peptide hormones, such as EGF, insulin, IGF, gastrin, bombesin and somatostatin(SST) which inhibits proliferation of gastrointestinal cancer cells, could regulate the proliferation of gastrointestinal cancer cells. The comprehensive biology functions of somatostatin and its analogues are mediated by the five somatostatin receptor subtypes expressing on the cell membrane, in which somatostatin receptor II(SSTR2) plays an important role in the anti-proliferation effects. SSTR2 inhibits proliferation of cancer cells directly by inducing G1 cell cycle arrest or apoptosis. As a result of the inhibition of secretion of growth-promoting hormones and growth factors, angiogenesis or blood supply to the tumor, indirect anti-proliferation can also be mediated by SSTR2. The aims of the study are to detect the expression of SSTR2 in the specimens of colorectal cancer patients and analyze the relationship between the expression and characteristics of the tumor, and to confirm the inhibition of somatostatin receptor agonist mediated by SSTR2 on the colon tumor cell growth in vitro and vivo and its effect on the migration of colon carcinoma cell in vitro. Furthmore the effect of somatostatin analogue on cell cycle regulating factor cyclin D1 is to be studied to explore the mechanism of inhibitory effect of somatostatin and its analogues on the proliferation of colon carcinoma cell, if the inhibitory effect was observed. Materials and methods1. SSTR2 mRNA dectection in the specimens of colorectal cancer patients. 48 inpatients diagnosed as colonic adenocarcinoma by histopathology from 1998 to 2000 were included. All tissue samples, including normal colonic mucosa, mucosa adjacent to the tumor, tumor, and/or lymph node, were collected immediately after surgical resection , frozen and stored at -80 ℃. The SSTR2 mRNA were detected with RT-PCR and hybridization in situ.2. The effect of the specific agonist and antagonist to SSTR2 on the proliferation of colon adenocarcinoma cell lines in vitro. Three colon-cancer cell lines HCT116, LOVO and SW480 of which cell proliferation was measured with MTT were treated with different...