NRP-1在卵巢癌增殖、迁移中的作用

Ovarian cancer is the most common of gynecological tumors. Although, the process of the proliferation and migration are not clear. The preliminary work indicated that NRP-1 was expressed in ovarian cancer tissue. Ovarian NRP-1 expression level was significantly higher in early recurrence patients compared to no recurrence patients. In this study, we will construct siRNA of NRP1 and KDR, which will indicate that NRP1 promote the combination of VEGF and VEGFR2 and facilitate the process of the proliferation and migration of ovarian cancer.siNRP1 and siKDR will be transfected in vitro and in vivo. The change of the protein and mRNA levels of NRP1, VEGF ,KDR and p130Cas will be detected. The change of the proliferation, migration and angiogenesis in tumors will also be detected. This study can offer a new spot for antiangiogenesis therapy of ovary cancer, and promote the targeting gene therapy of ovary cancer.

卵巢癌是妇科常见的三大恶性肿瘤之一，但其增值、迁徙的作用机制仍不清楚。课题前期工作提示，NRP-1存在于卵巢癌组织内，并且卵巢癌术后早期复发患者的NRP-1表达明显高于未复发患者。本项目拟构建NRP-1及KDR的siRNA，揭示NRP-1促进VEGF与VEGFR-2结合后促使卵巢癌增殖、迁移的作用机制。通过体内体外转染siNRP1及siKDR，检测NRP-1、VEGF、KDR、p130Cas蛋白、mRNA水平的改变，及对肿瘤增殖、迁移和肿瘤内新生血管形成的影响。此项目顺利实施，将为卵巢癌血管靶向治疗提供新的靶点，推动卵巢癌血管靶向基因治疗的发展。

卵巢癌是妇科常见的三大恶性肿瘤之一，是女性生殖系统肿瘤中最主要的致死原因。Neuropilin-1(NRP-1)是VEGF的新型受体。研究结果表明NRP-1可加强VEGF与VEGFR-2的结合, 能增强VEGF165介导内皮细胞趋化活性及有丝分裂原性,表明NRP-1是作为VEGF的协同受体发挥作用。VEGF促细胞存活、增生等重要作用主要都是通过NRP-1来完成的。本研究收集我院90例卵巢上皮癌、10例卵巢良性上皮肿瘤及6例正常卵巢标本，并进行了RT-PCR、Weatern和免疫组化的检测，结果表明NRP-1在上皮性卵巢癌表达增加，良性上皮性肿瘤内表达下降，上皮性卵巢癌与交界性上皮肿瘤相比无明显差异。构建siNRP-1质粒并转染卵巢癌细胞系，并比较卵巢癌细胞增殖、细胞周期、卵巢癌细胞迁移侵袭的影响。结果显示敲减NRP-1后可以抑制肿瘤细胞的增殖迁移，增加肿瘤细胞的凋亡。将转染siNRP-1的肿瘤细胞接种于裸鼠皮下形成皮下移植瘤，结果显示转染siNRP-1组肿瘤体积更小，并且移植瘤内超声造影显示新生血管明显减少。因此NRP-1参与卵巢癌的增殖迁徙和转移，敲减NRP-1的表达可以抑制卵巢上皮癌的增殖，NRP-1可作为卵巢癌治疗的靶点进一步深入研究。