花生四烯酸（AA）是一种必需脂肪酸，在慢性炎症和肿瘤发生中起着重要的作用，PTEN作为抑癌基因负向调节PI3K-AKT信号通路；AA和PTEN在结直肠肿瘤形成中的相互作用机制尚不清楚。我们前期研究发现COX-2和LOX抑制剂增加了PTEN表达，抑制PI3K-AKT及下游靶点的磷酸化，进而抑制了肿瘤的生长；但PTEN不依赖于COX-2和LOX自身代谢物的调节，而在AA处理的CT26结直肠癌细胞系中使用抗氧化剂却增强了PTEN的表达。基于前期报道中AA在COX-2和LOX代谢过程中增加了活性氧(ROS)的产生以及PTEN具有氧化失活的功能特点，我们推测ROS可能是AA-PTEN轴在结直肠肿瘤发生发展中的关键因素。本项目将通过体内外研究方案明确AA-ROS-PTEN轴在结直肠肿瘤形成中的作用及分子机制，为其个体化综合靶向治疗提供新的思路和理论依据。

Arachidonic acid(AA) is an essential fatty acid which plays an important role in the chronic inflammation and tumorigenesis, while PTEN acts as a tumor suppressor by negatively modulating the PI3K/AKT pathway. But the interaction mechanism of AA and PTEN in the colorectal tumorigenesis is unclear. Our recent research show that COX-2 inhibitor and LOX inhibitor increase the PTEN expression, inhibit PI3K-AKT.-mTOR pathway and its downstream phosphorylation, and supresse the tumor growth. Our further research find PTEN is independent on the metabolites of COX-2 and LOX themselves, while reactive oxygen species(ROS) scavengers do increase the PTEN expression during AA treatment for CT26 colorectal cancer cells. Based on the previous reports that AA increases ROS generation through COX-2 and LOX pathway. Further more, What is interesting is activity of PTEN is very fragile to oxidation according to another report. So we put forward the following hypothesis: ROS may be the key factor in the regulation of AA-PTEN axis for colorectal tumorgenesis. This project will deeply explore how AA-ROS-PTEN axis affects the colorectal tumorigenesis and their molecular mechanisms in vitro and in vivo experiments. The results of purposed experiments may find a novel strategy and theoretical foundation for the therapy targeting colorectal cancer.