新近研究表明血管生成素(ANG)能有效促进血管生成和肿瘤细胞增殖，在肿瘤发生发展中起重要作用。ANG通过核转位和激活PI3K/AKT/mTOR信号通路刺激rRNA转录和核糖体生成。体外实验证明核糖核酸酶抑制因子(RI)能与ANG结合而抑制其活性。然而，机制尚不清楚。前期工作发现RI具抑癌基因功能；RI与ANG在细胞内共定位；Co-IP初步证实其相互作用；RI与AKT磷酸化表达负相关。因此，推测RI可能结合ANG封锁其核转位和调控PI3K/AKT/mTOR信号通路及其相关通路cross-talk抑制肿瘤生长及转移。拟以膀胱癌为模型，明确RI与 ANG和PI3K/AKT通路的分子在细胞及临床标本中的表达与肿瘤细胞生长及转移的关系；获取RI与ANG在体内结合的直接证据及证实相互作用；在细胞和动物模型上探讨RI调节ANG活性、功能及其作用。旨在阐明RI抑制肿瘤的机制并为膀胱癌治疗提供新的分子靶点。

Recent research showed that Angiogenin (ANG) could effectively promote angiogenesis and tumor cell proliferation. ANG plays an important role in the development of cancer. ANG might stimulate ribosomal RNA transcription and the ribosome biogenesis through nuclear translocation and PI3K/Akt/mTOR signaling pathway. The experiment demonstrated that Ribonuclease inhibitor (RI) could inhibit ANG activity by binding to it in vitro. However, the underlying mechanism remains largely unknown to date. Our previous works suggest that RI might have tumor suppressor gene function. The experiments also showed that RI and ANG have a colocalization and interaction between them with Laser Scanning Confocal Microscope and Co-Immunoprecipitation. Moreover we found that RI and AKT phosphorylation express have a negative correlation. Therefore, we suppose that RI could block nuclear translocation of ANG and regulate PI3K/AKT signaling pathways and related signaling pathways cross-talk to inhibit tumor growth and metastasis. Using bladder cancer as a model, we would elucidate the relationships among the expressions of RI, ANG and PI3K/AKT pathways molecules and tumor growth as well as metastasis in cancer cells and clinical specimens; We are going to get direct evidence that RI could combine with ANG and to confirm their interaction in vivo; In addition, we will explore whether RI expression might adjust ANG activity，function and effects in vitro and in vivo. The purposes of our study are to further reveal the molecular mechanism of RI in inhibiting tumor growth and metastasis and to provide new molecule target for bladder cancer therapeutics.