Abstract

Erythropoietin-producing hepatocellular receptor A2 (EphA2) is upregulated in gastric cancer tissues and cells, which is accompanied by epithelial–mesenchymal transition (EMT). The current study was designed to establish the oxaliplatin-resistant human gastric cancer cell line SGC-7901/L-OHP, to determine if EMT in these cells could be reversed, and to determine if the susceptibility of these cells to oxaliplatin was affected by silencing EphA2 expression. We found that EphA2 expression levels were upregulated in gastric cancer and associated with chemotherapy sensitivity. EphA2 and the EMT molecular markers N-cadherin and Snail were upregulated in SGC-7901/L-OHP cells, while silencing of EphA2 using small interfering RNA had the opposite effect. Moreover, silencing of EphA2 inhibited cell migration and invasion, and significantly enhanced the sensitivity of oxaliplatin-resistant gastric cancer cells to oxaliplatin. These observations demonstrate that EphA2 affects the sensitivity to oxaliplatin by inducing EMT in oxaliplatin-resistant gastric cancer cells.

Highlights

  • Gastric cancer remains the third leading cause of cancer-related mortality worldwide; its incidence has decreased in the past six decades [1,2]

  • Erythropoietin-producing hepatocellular receptor A2 (EphA2) expression is associated with the therapeutic effects of oxaliplatin-based chemotherapy in patients with advanced gastric cancer

  • We revealed that EphA2 was overexpressed in gastric cancer patients who received chemotherapy

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Summary

Introduction

Gastric cancer remains the third leading cause of cancer-related mortality worldwide; its incidence has decreased in the past six decades [1,2]. Most patients are diagnosed with this disease at an advanced stage and the 5-year survival rate for surgically resected cases ranges from 13.1% to 43.8% [3]. Chemotherapeutic regimens for gastric cancer are continuously improving, adverse treatment effects following gastric cancer chemotherapy still occur in some patients. Resistance to chemotherapeutic drugs occurs or develops in most tumor cells, leading to treatment failure [8,9,10]. The 5-year survival rate of patients with advanced gastric cancer has not significantly increased [11,12,13]

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