CDO1通过PI3K/AKT信号通路调控胃癌细胞增殖及细胞周期

目的:探讨半胱氨酸双加氧酶1(CDO1)对胃癌细胞增殖、细胞周期的调控机制。方法:用脂质体法将si-NC组（转染si-NC）、si-CDO1组（转染si-CDO1）、pcDNA组（转染pcDNA）、pcDNA-CDO1组（转染pcDNA-CDO1）、pcDNA-CDO1+DMSO组（转染pcDNA-CDO1并用DMSO处理）、pcDNA-CDO1+IGF-1组（转染pcDNA-CDO1并用IGF-1处理）转染至AKG细胞。用实时荧光定量逆转录聚合酶链反应（qRT-PCR）、免疫印迹（Western blot）、细胞计数试剂盒（CCK-8）、流式细胞术检测细胞CDO1、PI3K、Akt、p-Akt蛋白的表达、细胞增殖、细胞周期。结果:与人胃黏膜上皮细胞GES-1相比,胃腺癌细胞AKG中CDO1的表达明显降低（P<0.05）;与si-NC组相比,si-CDO1组AKG细胞的增殖明显上调,细胞发生明显的S期、G2/M期阻滞,过表达CDO1则具有相反的作用。重要的是,敲减CDO1可上调PI3K/AKT信号通路关键基因PI3K、p-Akt的表达,而过表达CDO1具有相反的作用。激活PI3K/AKT信号通路后,过表达CDO1对胃癌细胞的增殖、细胞周期的调控作用可被部分逆转。结论:CDO1可抑制胃癌细胞的增殖,调控细胞周期,其机制与抑制PI3K/AKT信号通路的活性有关,将为胃癌的治疗提供参考。

CDO1 regulates gastric cancer cell proliferation and cell cycle through PI3K/AKT signaling pathway

Objective:To investigate the regulation mechanism of cysteine dioxygenase 1 (CDO1) on proliferation and cell cycle of gastric cancer cells.Methods:The si-NC group (transfected with si-NC),si-CDO1 group (transfected with si-CDO1),pcDNA group (transfected with pcDNA) and pcDNA-CDO1 group (transfected with pcDNA-CDO1).pcDNA-CDO1+DMSO group (transfected with pcDNA-CDO1 and treated with DMSO),pcDNA-CDO1+IGF-1 group (transfected with pcDNA-CDO1 and treated with IGF-1) were transfected into AKG cell with liposome method.The expression of CDO1,PI3K,Akt,p-Akt,cell proliferation and cell cycle were detected by qRT-PCR,Western blot,CCK-8 and flow cytometry.Results:Compared with human gastric epithelial cells GES-1,the expression of CDO1 in gastric adenocarcinoma cells AKG was significantly decreased (P<0.05).Compared with si-NC group,the proliferation of AKG cells in si-CDO1 group was significantly up-regulated,S phase,G2/M phase cells were blocked.Overexpression of CDO1 had the opposite effect.Importantly,knockdown of CDO1 up-regulated the expression of PI3K/p-Akt,a key gene in the PI3K/AKT signaling pathway,whereas overexpression of CDO1 had the opposite effect.After activation of PI3K/AKT signaling pathway,the overexpression of CDO1 can partially reverse the regulation of proliferation and cell cycle of gastric cancer cells.Conclusion:CDO1 can inhibit the proliferation of gastric cancer cells and regulate cell cycle.The mechanism is related to the inhibition of PI3K/AKT signaling pathway,which will provide a reference for the treatment of gastric cancer.