Expression of Somatostatin-Receptor and Inhibitory Effect of Somatostatin on Cell Proliferation in Hepatobiliary Malignancies

点击翻译按钮获取中文摘要

To evaluate the possibility of Somatostatin therapy for hepatobiliary tumors, molecular biological approaches were performed using MIN 6-cultured tumor cells in vitro. Cell proliferation was assessed by MTT assay, and mRNA expression of c-fos and c-jun by northern blotting and expression of Somatostatin receptor of hepatobiliary tumors by RT-PCR method. Our studies revealed the expression of Somatostatin receptor in MIN6 cells. It was shown that the proliferative activity of MIN6 cells was inhibited with the addition of Somatostatin into culture media. Furthermore, the expression of c-fos in MIN6 cells stimulated by serum was significantly suppressed by the pretreatment with Somatostatin. The expression of Somatostatin receptor was investigated in hepatobiliary tumors which were obtained as surgical specimen ; bile duct cancers in three, gallbladder carcinoma in one, hepatic cholangiocarcinoma in one. All these tumors were demonstrated to express only SSTR2, a subtype of Somatostatin r … More eceptor. Somatostatin was revealed to have inhibitory effects on cell proliferation through the mechanism that Somatostatin regulates the rate of cell proliferation by G-protein mediated signal transduction in MIN6 cells. The fact that hepatobiliary tumors have been shown to prossess Somatostatin receptor subtype, SSTR2, might suggest therapeutic implication of Somatostatin for hepatobiliary malignancies in clinical practice. It should be required to clarify the clinocopathological relationship between the expression of Somatostatin receptor and the various steps of tumor growth in hepatobiliary malignancies for the clinical application of Somatostatin therapy. At present, we are investigating its relationship using enough surgical samples including metastatic lymphnodes of hepatobiliary malignancies obtained in our institution. Our analysis has been clarifying how the expression of Somatostatin receptor affects biological events at molecular level of tumor invasion and metastasis in hepatobiliary malignancies. Therefore, further extensive investigations of this project should be required. Less