PI3K/Akt/mTOR信号通路与结直肠恶性肿瘤

PI3K / Akt / mTOR signaling pathway and colorectal malignant tumor

结直肠癌（colorectal cancer,CRC）是世界大多数地区最常见的恶性肿瘤之一。它的发展是一个多步骤过程,以改变正常细胞的分子信号为启动点,促进细胞发展,最终产生一种表型改变的恶性转化细胞。已有报道指出磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白[phosphatidylinositol-3-kinase（PI3K）/protein kinase B（Akt）/the mammalian target of Rapamycin（mTOR）,PI3K/Akt/mTOR]信号通路与结直肠恶性肿瘤产生有紧密的联系。也有报道证明约60%~70%的结直肠癌患者存在Akt信号的活化及PTEN的表达受损,进而说明PI3K/Akt/mTOR信号通路抑制药可以作为恶性肿瘤治疗的潜在靶点。近年来,PI3K/Akt/mTOR信号通路受到越来越多的关注,在不同的实验模型中利用针对这条通路的天然及合成药物来降低恶性肿瘤负荷。将近年来PI3K/Akt/mTOR信号通路在结直肠恶性肿瘤中的研究做一综述,并就今后结直肠恶性肿瘤中该通路可能的研究方向进行展望。

Colorectal cancer（CRC） is one of the most common cancers in most parts of the world. Its development is a multi-step process involving three distinct stages,i.e initiation that alters the molecular message of a normal cell,followed by promotion and progression that ultimately generates a phenotypically altered transformed malignant cell. Reports have suggested that between the PI3 K / Akt / mTOR signaling pathway and colorectal malignant tumor there have close contact. Activation of Akt signaling and impaired expression of phosphatase and tensin homolog（PTEN）（a negative regulator of Akt） has been reported in 60%-70% of human colon cancers and then inhibitors of PI3 K / Akt signaling have been suggested as potential therapeutic agents.Around 80% of human CRC possess mutations in the APC gene and half of the remainder feature β-catenin gene mutations which affect downstream signaling of the PI3 K / Akt pathway. In recent years,the PI3 K / Akt / mTOR signaling pathway has attracted more and more attention,and using natural and synthetic drugs to reduce the tumor burden in different experiment models. In this review authors review the role of PI3 K / Akt / mTOR and Wnt signaling in CRC,and make a prospect about the possible research directions in the future of this pathway in colorectal cancer.