脉络膜黑色素瘤是成年人最常见的眼内原发性恶性肿瘤。血管生成拟态与此类高侵袭性肿瘤的生长、转移及预后密切相关。我们的前期研究结果显示：新型多肽ZY1（PCT国际专利已进入实审），可抑制脉络膜黑色素瘤细胞的增殖、迁移和管腔形成，并可通过抑制脉络膜黑色素瘤内血管生成拟态的形成从而遏止肿瘤生长，初步机制研究发现ZY1可下调芳香烃受体核转位蛋白（ARNT）及ephrin受体A2（EphA2）的蛋白表达。本课题将以上述发现为基础，通过构建ARNT过表达载体、siRNA干扰，染色质免疫共沉淀等进一步揭示ZY1抑制肿瘤血管生成拟态的作用机制与ARNT/EphA2的关系；并利用免疫共沉淀等技术探讨ZY1作用于ARNT/EphA2的信号转导通路。本课题旨在从分子机理方面阐释该多肽抑制高侵袭性脉络膜黑色素瘤血管生成拟态的作用机制，可望为治疗高侵袭性脉络膜黑色素瘤开辟新的途径，具有临床成果转化的价值。

Choroidal melanoma is the most common primary malignant ocular tumor in adults. Vasculogenic mimicry (VM) is closely associated with tumor growth, aggressiveness, poor clinical outcome, and high risk of recurrence in patients with choroidal melanoma.Our recent study identified a novel peptide, named ZY1 (International Patent No: PCT/CN2011/076761), which exerts an anti-VM activity in vitro and arrests the growth of choroidal melanoma by inhibiting tumor VM. Our further investigation demonstrated that ZY1 could down-regulate the expression of aryl hydrocarbon receptor nuclear translocator (ARNT) and ephrin type-A receptor 2 (EphA2). Based on the findings, this study is designed to clarify the relationship between the anti-VM activity of ZY1 and ARNT/EphA2 via gene recombination technologies of ARNT, ChIPs and etc; and is also to elucidate the signal transduction pathways of ARNT/EphA2 after ZY1 applied. Following our previous work, the study is aimed to explore the molecular mechanisms of the anti-VM effect of peptide ZY1 in choroidal melanoma. Taken together, the research results may identify a novel small peptide, which provides a reasonable alternative for the treatment of choroidal melanoma.