Anti-LeY antibody enhances therapeutic efficacy of celecoxib against gastric cancer by downregulation of MAPKs/COX-2 signaling pathway: correlation with clinical study

Faisal Aziz, Xuesong Yang, Xiao-Qi Wang, Qiu Yan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Introduction: Helicobacter pylori (H. pylori) is a major causative agent for the induction of chronic gastritis, gastric ulcer and gastric cancer. Celecoxib (COX-2 inhibitor) inhibits gastric cancer cell proliferation, but with low treatment efficacy, limiting its applications. It is important to develop a better strategy to improve the efficacy of celecoxib. Lewis Y (LeY) is a difucosylated oligosaccharide, highly expressed in 60–90 % of human epithelial cancers, including gastric cancer. We previously found that H. pylori infection was associated with high level of LeY in gastric cancer. Material and Methods: Herein, we analyzed the correlation between H. pylori and cyclo-oxygenase-2 (COX-2), LeY, gastric markers (CA724 and GRN) in gastric patient’s tissue and serum samples by IHC and ELISA. Furthermore, we treated the primary gastric cancer cells with celecoxib, anti-LeY antibody or the combination, and analyzed their therapeutic efficacy on CA724, GRN and COX-2 expression by Western blot, flow cytometry and ELISA. Results: We found that gastric cancer had significantly high expression of H. pylori, COX-2, CA724, and GRN compared to gastric ulcers and chronic gastritis (P < 0.0001). H. pylori level showed significant correlation with COX-2 (R—0.552), LeY (R—0.861), CA724 (R—0.714) and GRN (R—0.664) (P < 0.0001). Additionally, the combination therapy led to impressive inhibition of gastric cancer cell proliferation, with decreased expression of COX-2, CA724 and GRN through downregulation of MAPKs/COX-2 pathway (P < 0.01). Conclusions: Our findings suggest that anti-LeY antibody enhances the cancer cell proliferation inhibitory effects of celecoxib, which might be a new feasible way for gastric cancer therapy.

Original languageEnglish (US)
Article number9
Pages (from-to)1221-1235
Number of pages15
JournalJournal of Cancer Research and Clinical Oncology
Volume141
Issue number7
DOIs
StatePublished - Jul 22 2015

Keywords

  • Anti-LeY antibody
  • COX-2
  • Celecoxib
  • Cell proliferation
  • Gastric cancer
  • Helicobacter pylori

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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