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

生长抑素受体在肝胆肿瘤中的表达及其对细胞增殖的抑制作用

基本信息

批准号：
10671156
负责人：
MIYAZAKI Masaru
金额：
$ 2.43万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

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

为探讨生长抑素治疗肝胆肿瘤的可能性，采用体外培养的肝癌细胞MIN 6，从分子生物学角度对生长抑素治疗肝胆肿瘤进行了研究。MTT法检测细胞增殖，北方印迹法检测c-fos、c-jun mRNA表达，RT-PCR法检测生长抑素受体表达。我们的研究揭示了生长抑素受体在MIN 6细胞中的表达。结果表明，生长抑素对MIN 6细胞的增殖活性有明显的抑制作用。生长抑素预处理可明显抑制血清刺激的MIN 6细胞c-fos表达。本文报道了生长抑素受体在肝胆肿瘤中的表达，其中胆管癌3例，胆囊癌1例，肝胆管癌1例。所有这些肿瘤都被证明只表达SSTR 2，SSTR 2是生长抑素的一种亚型。 ...更多信息受体。生长抑素通过G蛋白介导的信号转导调节细胞增殖速率，从而抑制细胞增殖。生长抑素受体亚型SSTR 2在肝胆肿瘤中的表达，提示生长抑素对肝胆恶性肿瘤的临床治疗意义。生长抑素治疗的临床应用需要明确生长抑素受体表达与肝胆恶性肿瘤生长各阶段的临床病理关系。目前，我们正在使用足够的手术样本，包括在我们机构获得的肝胆恶性肿瘤转移淋巴结，来研究它们之间的关系。我们的分析阐明了生长抑素受体的表达如何在分子水平上影响肿瘤侵袭和转移的生物学事件。因此，需要对该项目进行进一步广泛的调查。少