Akt／FoxO传导通路调节细胞凋亡作用的研究进展

Role of Akt/FoxO pathway in regulation of cell apoptosis

Foxo转录因子是PKB／Akt的下游靶点。Akt调节细胞生存和增殖。Akt磷酸化Foxo抑制Fox0的转录功能，促进细胞生存、生长和增殖。在癌症中FoxO在不同的细胞信号通路中发挥重要作用。FoxO通过两个途径抑制凋亡信号，促进细胞生长，其包括线粒体靶点蛋白Bcll2家族的多种前凋亡成员的表达、死亡受体配体如Fas配体和肿瘤坏死因子相关凋亡诱导配体（TRAIL）的表达，或是增加各种细胞周期蛋白依赖性激酶抑制蛋白的水平。本文主要概括了Akt／FoxO调节细胞生长和生存的机制，以期为抗癌治疗提供新的可能。

The transcription factor FoxO is a downstream target of PKB/Akt that regulates cell survival and proliferation. Phosphorylation of FoxO by Akt inhibits its own transcriptional function and thus promotes cell survival, growth and proliferation. Substantial evidence showed that FoxO plays vital roles in diverse cellular signaling pathways that are implicated in cancer. There are two means by which FoxO inhibited cell apoptosis and promoted cell growth. One means is to regulate the expression of members of mitochondrial Bcl 12 family, Fas ligands and tumor necrosis factor related apoptosis inducing ligand （TRAIL）. The other is to enhance the level of cyclin-dependent kinase inhibitors. In this paper, we reviewed the underlying mechanisms of the involvement of Akt/FoxO in the regulation of cell survival and growth in order to provide new options for anti-tumor therapy.