Effect of Helicobacter pylori Lipopolysaccharide on Malignant Transformation of Gastric Epithelial Cells by Regulating MDM2 Expression
10.3969/j.issn.1008-7125.2019.08.004
- VernacularTitle: 幽门螺杆菌脂多糖通过调节MDM2表达对胃上皮细胞恶性转化的影响
- Author:
Yuqin LI
1
Author Information
1. Department of Gastroenterology, Shanghai Pudong Hospital, Fudan University
- Publication Type:Journal Article
- Keywords:
Helicobacter pylori;
Lipopolysaccharides;
Proto-Oncogene Proteins c-mdm2;
Stomach Neoplasms
- From:
Chinese Journal of Gastroenterology
2019;24(8):465-470
- CountryChina
- Language:Chinese
-
Abstract:
Background: Helicobacter pylori lipopolysaccharide (Hp-LPS) plays an important role in gastric carcinogenesis. Aims: To investigate the regulatory effect of Hp-LPS on MDM2 gene expression and its impact on malignant transformation of gastric epithelial cells. Methods: After stimulated with Hp-LPS 1 μg/mL or Escherichia coli (E. coli)-LPS 1 μg/mL for 24 hours, expression of MDM2 in human gastric epithelial cell line (GES-1) and gastric cancer cell line (HGC-27 and MKN45) was detected by Western blotting. Plasmid containing MDM2 promoter luciferase reporter gene was constructed and transfected into HGC-27 cells, and the relative luciferase activity was measured after treated with Hp-LPS for 24 hours. RNA interference plasmid targeting to MDM2 was constructed and transfected into GES-1, HGC-27, and MKN45 cells, then changes in cell apoptosis and invasiveness were analyzed by flow cytometry and Transwell invasion assay. Growth inhibition of MKN45 and HGC-27 xenograft tumors in nude mice was observed after receiving caudal vein injection of siRNA-hMDMA2-3 for silencing MDM2 expression. Results: Hp-LPS enhanced the transcriptional activity of MDM2 promoter and up-regulated MDM2 protein expression in gastric epithelial and gastric cancer cells. In GES-1, HGC-27, and MKN45 cells transfected with siRNA-hMDMA2-3, the cell apoptosis was increased and the cell invasive capacity was reduced as compared with those transfected with negative control siRNA (P<0.05). Furthermore, the tumor inhibition rate of nude mice treated with siRNA-hMDMA2-3 was increased significantly as compared with those treated with negative control siRNA (P<0.05). Conclusions: Hp-LPS can induce malignant transformation of gastric epithelial cells by up-regulating MDM2 expression. Inhibiting MDM2 expression might suppress the malignant transformation and tumor growth by inducing cell apoptosis and reducing cell invasiveness.
