基于PI3K/AKT/mTOR和ERK/MAPK双信号通路探讨PAP-2抗肺癌机制研究

肺癌是全球发病率最高的恶性肿瘤，已成为肿瘤相关死亡的首要病因。随着国家工业化、城镇化推进，导致雾霾日益加重，肺癌在我国成为全球重灾区。目前肺癌的治疗效果较差，长期化疗损害重要脏器且会产生耐药。因此，寻找低毒、高效新型抗癌药物势在必行。项目申请人在研究肺癌发生、转移及相关基因表达基础上，从双齿围沙蚕中筛选得到分子量为1080 Da、化学结构明确的活性多肽PAP-2，经前期体内外研究有显著诱导肺癌胞凋亡和基因调控作用。现将PAP-2作用于肺癌细胞株H1299，基于PI3K/AKT/mTOR和ERK/MAPK双信号通路，明确其药物靶点；研究PAP-2体内对肺癌H1299裸鼠移植瘤模型的药效学实验，探讨PAP-2抗肺癌机制，阐明其抗肺癌效果和相关基因表达。本研究为研发一种具有自主知识产权的抗肺癌海洋肽类药物的研发奠定基础。因此，具有重要的学术价值和良好的应用前景。

Lung cancer is one of the most common and fatal cancers in the world. The incidence and mortality of lung cancer in China has increased because of smoking and increased air pollution with the constant promotion of industrialization and urbanization. Currently, the treatment effect of lung cancer is poor and the long-term chemotherapy can damage the vital organs and cause drug resistance. Therefore, the research and development of more effective and less toxic antitumor drugs from natural sources is necessary. Based on the study of lung cancer occurrence, metastasis and related gene expression, an anti-cancer peptide PAP-2 with a molecular weight of 1080 Da was obtained from Perineries aibuhitensis by enzymolysis and purification strategies. In vitro and in vivo studies also showed it has significant effects on apoptosis and gene regulation of lung cancer cells. In this study, PAP-2 will be used to lung cancer cells H1299 to elucidate its drug targets and anti-lung cancer mechanisms on the basis of PI3K/AKT/mTOR and ERK/MAPK pathway. H1299 nude-mouse transplanted tumor model will also be established to explore the effects of PAP-2 and its anti-lung cancer mechanism in vivo .The program lays the foundation for the development of a research and development with independent intellectual property rights of marine peptide drugs against lung cancer. Therefore, it has important academic values and good application prospect.