Department of Gastroenterology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
J Cell Biochem. 2018 Dec;119(12):9997-10004. doi: 10.1002/jcb.27329. Epub 2018 Aug 26.
Gastric cancers are a group of highly aggressive malignancies with a huge disease burden worldwide. Gastric infections, such as helicobacter pylori, can induce the occurrence of gastric cancers. However, the role of gastric infection in gastric cancer development is unclear. Programmed death-ligand 1 (PD-L1, B7-H1) is a member of the B7 family of cell surface ligands, which binds the PD-1 transmembrane receptor and inhibits T-cell activation within cancer tissues. It has been reported that the expression of PD-L1 is inversely related to the prognosis of patients with gastric cancers. Therefore, the regulation of PD-L1 expression in gastric cancers needs to be studied. In the current study, we explored the possible effects of lipopolysaccharide (LPS) on PD-L1 expression in gastric cancer cells. We observed that LPS stimulation could markedly increase PD-L1 expression in gastric cancer cells. Furthermore, we found that nuclear factor-κB (NF-κB) activation was involved in PD-L1 expression in gastric cancer cells exposed to LPS stimulation through p65-binding to the PD-L1 promoter. Taken together, these data indicate that gastric infection might promote the development of gastric cancers thought the LPS-NF-κB-PD-L1 axis.
胃癌是一组具有高度侵袭性的恶性肿瘤,在全球范围内疾病负担巨大。胃感染,如幽门螺杆菌,可以诱导胃癌的发生。然而,胃感染在胃癌发展中的作用尚不清楚。程序性死亡配体 1(PD-L1,B7-H1)是细胞表面配体 B7 家族的成员,它与 PD-1 跨膜受体结合,抑制癌症组织内 T 细胞的激活。据报道,PD-L1 的表达与胃癌患者的预后呈负相关。因此,需要研究胃癌中 PD-L1 表达的调控。在本研究中,我们探讨了脂多糖(LPS)对胃癌细胞中 PD-L1 表达的可能影响。我们观察到 LPS 刺激可显著增加胃癌细胞中 PD-L1 的表达。此外,我们发现核因子-κB(NF-κB)的激活参与了 LPS 刺激诱导的胃癌细胞中 PD-L1 的表达,通过 p65 与 PD-L1 启动子结合。综上所述,这些数据表明,胃感染可能通过 LPS-NF-κB-PD-L1 轴促进胃癌的发展。