血管新生在实体瘤生长和转移过程中具有重要作用。我们前期将V1肽(ATWLPPR) 和V2肽(NLLMAAS) 通过柔性连接子Ala-Ala (AA) 连接起来构建一条新的生物活性肽V3 (ATWLPPRAANLLMAAS)。在鼠源性S180和H22裸鼠移植瘤模型中，V3肽具有比V1、V2肽更强的抗肿瘤和抑制血管新生的作用，但V3肽的分子靶点、作用信号通路以及对人源性肿瘤生长的抑制作用尚不明确。本项目主要通过体内外实验研究V3肽抑制HepG2、 HuH7和SMMC-7721肝癌生长与血管新生的作用，采用放射性配体-受体结合实验、分子对接和分子动力学模拟技术研究V3肽的分子靶点，采用Western Blot技术检测V3肽是否通过Ras/Raf/MEK/ERK信号通路发挥抑制肝癌血管新生和诱导肝癌细胞凋亡的作用，从而阐明V3肽对肝癌生长的抑制作用及其分子机制，为进一步将其应用于临床研究奠定基础。

Angiogenesis plays important roles in the growth and metastasis of solid tumors. We have previously connected peptide V1 (ATWLPPR) with peptide V2 (NLLMAAS) via a flexible linker Ala-Ala (AA) to construct a novel bioactive peptide V3 (ATWLPPRAANLLMAAS), which has shown more potent antitumor and antiangiogenic effects than peptide V1 and V2 on murine S180 and H22 xenografts bearing nude mice. However, the molecular target and the signalling pathway of inhibitory effect of peptide V3 on human tumors are still unknown. In this project, we will mainly focus on the antitumor and antiangiogenic effects of peptide V3 on HepG2, HuH7, and SMMC-7721 hepatoma cell lines both in vitro and in vivo. The radioactive ligand-receptor binding assays, molecular docking, and molecular dynamics simulation will be adopted to explore the molecular target of peptide V3. Furthermore, Western blot analysis will be used to detect whether peptide V3 could exert antiangiogenic and apoptosis-induced effects through the Ras / Raf / MEK / ERK pathway. This project will provide insights into understanding the inhibitory effect & molecular mechanism of peptide V3 on hepatocellular carcinoma, which will lay the foundation for its further application in clinical research.