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

为探讨生长抑素治疗肝胆肿瘤的可能性，采用体外培养的Min-6肿瘤细胞进行分子生物学研究。用四甲基偶氮唑盐比色法检测细胞增殖，Northern印迹法检测c-fos、c-jun基因的表达，RT-PCR法检测生长抑素受体的表达。我们的研究揭示了生长抑素受体在MIN6细胞中的表达。结果表明，在培养液中加入生长抑素可抑制MIN6细胞的增殖活性。此外，生长抑素可显著抑制血清刺激的MIN6细胞c-fos的表达。应用免疫组织化学方法检测了3例胆管癌、1例胆囊癌、1例肝胆管细胞癌组织中生长抑素受体的表达。所有这些肿瘤都被证实只表达生长抑素r…的一个亚型sstr2。更多的感受器。生长抑素通过G蛋白介导的信号转导调节细胞增殖速度，从而抑制细胞增殖。肝胆肿瘤存在生长抑素受体亚型SSTR2，提示生长抑素治疗肝胆恶性肿瘤具有临床意义。为临床应用生长抑素治疗，有必要明确生长抑素受体的表达与肝胆恶性肿瘤肿瘤生长各阶段的临床病理关系。目前，我们正在使用足够多的手术标本，包括在我所获得的肝胆恶性肿瘤的转移淋巴结，来研究它们之间的关系。我们的分析一直在阐明生长抑素受体的表达如何在分子水平影响肝胆恶性肿瘤肿瘤侵袭和转移的生物学事件。因此，需要对这一项目进行进一步的广泛调查。较少

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