美洲大蠊多肽对肝癌微环境的影响

本项目是在申请人前期获得了美洲大蠊抗肿瘤活性物质CⅡ-3较好的对抗H22 肝癌移植瘤的前提下，进一步从CⅡ-3获得了PAP系列多肽分子。该项研究拟在以人肝癌细胞HepG2为研究对象，应用美洲大蠊PAP1-3三个多肽进行体内外干预，采用细胞形态学、RT-PCR 法、Western blotting法、ELASA法等多种实验技术，分别从细胞和分子水平来探讨美洲大蠊PAP1-3三个多肽对肝癌的微环境是否存在抗缺氧、影响肿瘤的血管形成以及对抗肿瘤免疫微环境等，以评估美洲大蠊PAP1-3三个多肽在调控肝癌微环境时的作用机制及结构基础，旨在为多肽类抗肿瘤药物的开发提供新的理论参考。

In our series studies, we have successively obtained antitumor active substances, including the bioactive extract CII-3, chemical entities PAP series of polypeptide molecules from Periplaneta americana. It was found that CII-3 possessed inhibitory effect on hepatoma cell line H22. In order to explore the possible mechanism of action of CII-3, we adopt three polypeptides PAP1, PAP2, and PAP3 isolated from CII-3 as study subjects to systematically evaluate the effects of above-mentioned polypeptides. With the application of morphology study, RT-PCR equipment, ELASA and Western blotting techniques, we aims to investigate the anti hypoxia, anti-angiogenesis, and immunoregulation of PAP1 - PAP3 in the microenvironment of hepatocellular carcinoma HepG2 cells in vitro and in vivo on both cell and molecular levels. With the objectives of clarifying the mechanism of action along with the structural foundation of PAP1 - PAP3 Periplaneta americana, it is very feasible to provide a theoretical reference for the research and development of novel polypeptide antitumor agents.