无功能腺瘤是一种常见的垂体腺瘤，严重危害患者的健康及生活质量，目前缺乏有效的药物治疗，针对其发病机制进行深入研究寻找理想的治疗靶点具有重要的临床意义。Notch通路和多种肿瘤的发生发展密切相关，其阻断剂γ分泌酶抑制剂可以在体内外试验中抑制多种Notch通路相关肿瘤的生长、增殖。我们在既往的研究中证明无功能腺瘤中Notch3及其配体Jagged-1表达升高，结合既往大量研究提示Notch信号通路在无功能腺瘤发生、发展中可能有重要作用。但目前的研究仅限于Notch受体，缺乏通路中配体、靶基因及阻断剂在无功能腺瘤中作用及其机制的阐述。本研究拟对Notch通路在无功能腺瘤中的作用做一系统性研究，阐明Notch通路在无功能腺瘤发生发展中的作用并探讨可能的机制；同时在体内、外试验中研究其阻断剂对无功能腺瘤的调节作用并探索可能的机制，旨在为无功能腺瘤的药物治疗提供理论依据。

Non-functioning pituitary adenomas(NFPAs) are relatively common. Clinically recognized non-functioning pituitary adenomas constitute approximately one-third of all tumours of the anterior pituitary. Non-functioning pituitary tumours are mostly of gonadotroph cell origin and are devoid of humoral hypersecretory syndromes. They are usually large at the time of diagnosis, commonly presenting with headaches, visual ?eld defects and hypopituitarism. The best treatment options remain neurosurgery and radiation therapy. Unfortunately, although several clinical studies have been carried out, no clear effective medical therapy for these tumours has emerged. Therefore, more speci?c and effective drugs must be developed for the medical treatment of non-functioning pituitary adenomas. The fundamental mechanisms of NFPAs tumorigenesis involve the cell cycle regulation, oncogene, tumor suppressor gene et.c. Recently, three further oncogenic pathways have been implicated in NFPAs tumorigenesis: the Ras-BRAF-mitogen-activated protein kinase (MAPK) pathway, the Wnt signalling pathway and the maternally expressed gene 3 (MEG3). Recent study has showed that Notch pathway was overexpressed in NFPAs other than in normal human pituitary tissue and hormone-secreting pituitary adenomas. The fundamental mechanisms of Notch proteins involve the regulation of various aspects of cell differentiation, proliferation and apoptosis. And Notch pathway is proved to be has crosstalk with MAPK pathway and Wnt pathway. Increasing evidence suggests that abnormal Notch signalling also contributes to the pathogenesis of various human tumors, such as pancreatic, ovarian, and lungcancers. Gamma-secretase inhibitor (GSI) is a inhibitor of Notch signalling pathway. GSI can reduce tumor cell proliferation, inhibite serum independence, and induce apoptosis in various tumors through inhibiting of Notch signalling pathway. Although several studies have suggested that Notch pathway may play a important role in the tumorigenesis of NFPAs, further studies are needed to elucidate the function of Notch pathway in the pathogenesis of human non-functioning pituitary adenomas and whether GSI can reduce tumor cell proliferation and induce apoptosis in NFPAs. Our study provide the ?rst comprehensive analysis of the expression of Notch signaling pathways in NFPAs and for the first time determine the effects of GSI on tumor cell growth, proliferation, apoptosis and hormone secreting of NFPAs in vitro and in vivo. Our study will provides new insights into the pathogenesis of human non-functioning pituitary adenomas and implicates the Notch pathway and its antagonist as a molecular therapeutic target for the treatment of NFPAs.