垂体腺瘤是最常见的颅内肿瘤之一，目前尚缺乏针对缩小肿瘤体积、诱导细胞凋亡的有效药物。我们从南海海洋微生物的次代谢产物中，筛选到一种新颖蒽环类化合物—SZ-685C。我们前期发现SZ-685C能够抑制多种垂体腺瘤细胞增殖并诱导其凋亡，那么其诱导细胞凋亡的机制是什么？进一步实验显示：①SZ-685C引起miR-200c表达下调，PTEN表达上调；②生物信息学和荧光素酶证实miR-200c和PTEN具有直接靶向关系；③抑制miR-200c可促进细胞凋亡，且PTEN表达升高，p-Akt表达降低。于是我们设想SZ-685C诱导垂体腺瘤细胞的凋亡是由于miR-200c靶向调节PTEN/Akt而产生。申请人拟采用腺病毒、免疫电镜、激光共聚焦等工具，结合多种细胞和动物模型，旨在阐明SZ-685C通过miR-200c调控PTEN/Akt通路诱导腺瘤细胞凋亡的分子机制，为临床治疗垂体腺瘤提供优质的候选药物。

pituitary adenoma is one of the most common intracranial tumors, and so far there is no effective drug to reduce tumor volume, induced tumor cells apoptosis.We have screened a novel anthracycline derivative，SZ-685C,from Secondary metabolite of marine microorganisms of the south China sea.Our previous study found that SZ-685C could inhibit various pituitary tumor cell proliferation and induce it apoptosis,so what is the mechanism of cell apoptosis? Our further research found ①SZ-685C caused the down-regulation of miR-200c and up-regulation of PTEN;② Bioinformatics and luciferase experiments demonstrated that miR-200c was directly targeted with PTEN;③ inhibition of miR-200c could promote tumor cell apoptosis,the expression of PTEN increased and p-Akt decreased.Therefore,we propose the hypothesis that the reason why SZ-685C induce the tumor cell apoptosis is because miR-200c directly targeted PTEN/Akt.The applicant intends to clarify molecular mechanism whether SZ-685C induce the pituitary adenoma cell apoptosis through miR-200c directly targeted PTEN/Akt,and provide high quality candidate drugs for clinical treatment of pituitary adenoma by using adenovirus, immune electron microscope and laser confocal microscope and other tools,combining various cell and animal model.