Scholarlink

Background <p>The lipopolysaccharide (LPS) of <i>Helicobacter pylori</i> (HP) is a critical virulence factor in gastric cancer development. As a toxic component of the HP cytoderm, HP LPS causes persistent inflammatory injury to the gastric mucosa. Although HP lipopolysaccharide exhibits weaker endotoxic activity, it still promotes gastric cancer progression by inducing chronic inflammation and enhancing cellular proliferation. However, the specific signaling pathways involved are not fully understood.</p> Methods <p>GES-1, HGC-27, and MKN-45 cells were treated with LPS from HP and <i>E. coli</i>. Western blotting and a luciferase reporter assay were used to analyze MDM2 expression and transcriptional activity. Cell proliferation, migration, and invasion were evaluated through colony formation, scratch wound healing, and transwell assays. Immunohistochemistry was used to examine MDM2 and p53 expression, while immunofluorescence detected regulatory T cells. Gastric cancer mouse models were also used to confirm MDM2’s role in gastric cancer.</p> Results <p>HP infection resulted in elevated MDM2 levels in gastric precancerous lesions and cancers. HP LPS enhances MDM2 expression in GC cells<b>.</b> This effect is mediated through TLR4/MAPK/AP-1, which promotes the proliferation and invasion of gastric cancer cells. In addition, MDM2 participated in Tregs infiltration and promoted the maintenance of an immunosuppressive tumor microenvironment in gastric cancer.</p> Conclusions <p>HP LPS enhances MDM2 expression in GC cells through the TLR4/MAPK/AP-1 pathway. MDM2 mediates the protumor effects of HP LPS by promoting tumor cell proliferation and regulating Treg-mediated immune suppression. Our study deepens the understanding of gastric cancer progression and identifies MDM2 as an effective therapeutic target.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Helicobacter pylori Lipopolysaccharide Upregulates MDM2 via the TLR4/MAPK/AP-1 Pathway to Promote Gastric Cancer Progression

  • 期刊论文

  • 发表日期：

    2025年11月29日

查看全文
  • Yuqin Li,
  • Lin Xu,
  • Xiaolan Lu,
  • Baiqing Fu,
  • Qiuyu Jiang,
  • Wujun Xiong,
  • Wenqing Tang,
  • Dejun Wu

摘要

Background

The lipopolysaccharide (LPS) of Helicobacter pylori (HP) is a critical virulence factor in gastric cancer development. As a toxic component of the HP cytoderm, HP LPS causes persistent inflammatory injury to the gastric mucosa. Although HP lipopolysaccharide exhibits weaker endotoxic activity, it still promotes gastric cancer progression by inducing chronic inflammation and enhancing cellular proliferation. However, the specific signaling pathways involved are not fully understood.

Methods

GES-1, HGC-27, and MKN-45 cells were treated with LPS from HP and E. coli. Western blotting and a luciferase reporter assay were used to analyze MDM2 expression and transcriptional activity. Cell proliferation, migration, and invasion were evaluated through colony formation, scratch wound healing, and transwell assays. Immunohistochemistry was used to examine MDM2 and p53 expression, while immunofluorescence detected regulatory T cells. Gastric cancer mouse models were also used to confirm MDM2’s role in gastric cancer.

Results

HP infection resulted in elevated MDM2 levels in gastric precancerous lesions and cancers. HP LPS enhances MDM2 expression in GC cells. This effect is mediated through TLR4/MAPK/AP-1, which promotes the proliferation and invasion of gastric cancer cells. In addition, MDM2 participated in Tregs infiltration and promoted the maintenance of an immunosuppressive tumor microenvironment in gastric cancer.

Conclusions

HP LPS enhances MDM2 expression in GC cells through the TLR4/MAPK/AP-1 pathway. MDM2 mediates the protumor effects of HP LPS by promoting tumor cell proliferation and regulating Treg-mediated immune suppression. Our study deepens the understanding of gastric cancer progression and identifies MDM2 as an effective therapeutic target.