Clinical Laboratory Center, Jiangsu Taizhou People's Hospital, Taizhou, Jiangsu, People's Republic of China.
School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
Mol Biol Rep. 2021 Jan;48(1):611-621. doi: 10.1007/s11033-020-06105-y. Epub 2021 Jan 3.
Previous research has demonstrated a correlation between elevated expression of Fos-related antigen 1 (FRA-1) and malignancies. Nevertheless, the role of FRA-1 in Helicobacter pylori infected gastric cancer cells remains vague. Our study aims to investigate whether FRA-1 plays a role in the apoptosis of MGC-803 induced by H. pylori and possible mechanisms. MGC-803 cells were used in vitro to establish a cell model of H. pylori infection. After stimulation with H. pylori, the expression of FRA-1 was increased in MGC-803 cells. H. pylori infection promoted the apoptosis of MGC-803 cells, and led to cell cycle arrest and increased oxidative stress levels. Furthermore, the knockdown of FRA-1 reinforced these changes. H. pylori decreased the expression of Bcl2, Caspase3 and Caspase9, while increased the level of BAX, Cleaved-Caspase3 and Cleaved-Caspase9; in addition, it led to the decrease of major proteins in Ras/Erk and PI3K/AKT signaling pathway. As expected, these changes were augmented by FRA-1 knockdown. Our results demonstrated that high expression of FRA-1 induced by H. pylori suppresses apoptosis in MGC-803 cells which may be regulated by oxidative stress and cycle arrest through caspase family, Ras/Erk and PI3K/AKT signaling pathway.
先前的研究表明,Fos 相关抗原 1(FRA-1)的高表达与恶性肿瘤之间存在相关性。然而,FRA-1 在幽门螺杆菌感染的胃癌细胞中的作用仍不清楚。本研究旨在探讨 FRA-1 是否在幽门螺杆菌诱导的 MGC-803 细胞凋亡中发挥作用及其可能的机制。我们在体外使用 MGC-803 细胞建立了幽门螺杆菌感染的细胞模型。在受到幽门螺杆菌刺激后,MGC-803 细胞中 FRA-1 的表达增加。幽门螺杆菌感染促进了 MGC-803 细胞的凋亡,并导致细胞周期停滞和氧化应激水平升高。此外,FRA-1 的敲低加强了这些变化。幽门螺杆菌降低了 Bcl2、Caspase3 和 Caspase9 的表达,同时增加了 BAX、Cleaved-Caspase3 和 Cleaved-Caspase9 的水平;此外,它还导致 Ras/Erk 和 PI3K/AKT 信号通路中的主要蛋白减少。正如预期的那样,FRA-1 的敲低增强了这些变化。我们的结果表明,幽门螺杆菌诱导的 FRA-1 高表达抑制了 MGC-803 细胞的凋亡,这可能是通过半胱天冬酶家族、Ras/Erk 和 PI3K/AKT 信号通路调节氧化应激和细胞周期停滞来实现的。