Remifentanil Inhibits the MAPK/ERK Pathway to Attenuate Malignant Biological Behaviors of Esophagogastric Junction Adenocarcinoma Cell Line AGS

ZHU Xiaoyan¹, WANG Li¹*, GUO Dan², CUI Dapeng², WANG Ruifeng², LIU Weishu^1,3, YANG Yixuan²

(¹Department of Anesthesiology, the First Hospital Affiliated to North China University of Science and Technology, Zhangjiakou 075000, China; ²Department of Hepatobiliary Surgery, the First Hospital Affiliated to North China University of Science and Technology, Zhangjiakou 075000, China; ³Department of Hepatobiliary and Pediatric Surgery, the First Hospital Affiliated to North China University of Science and Technology, Zhangjiakou 075000, China)

Abstract:

This study aims to investigate whether remifentanil can inhibit the malignant biological behavior of esophagogastric junction adenocarcinoma cells by regulating the MAPK (mitogen-activated protein kinase)/ERK (extracellular signal-regulated kinase) pathway, thereby suppressing proliferation, migration, and invasion. Human gastric adenocarcinoma AGS cells were divided into five groups: control, low-, medium-, and high-dose remifentanil groups (50, 100, 200 nmol/L remifentanil), and remifentanil plus MAPK/ERK activator group (200 nmol/L remifentanil+5 μmol/L C16-PAF). This article assessed AGS cell proliferation, migration, invasion, apoptosis, cell cycle arrest, MAPK mRNA, ERK mRNA, PCNA (proliferating cell nuclear antigen), E-cadherin, N-cadherin, MAPK/ERK pathway- related proteins, downstream signaling proteins c-Fos and c-Jun, and apoptosis-related proteins. The results showed that compared with the control group, the 50, 100, and 200 nmol/L remifentanil groups exhibited decreased D-values, EdU-positive cell rates, cell migration rates, numbers of invasive cells, MAPK mRNA, ERK mRNA, PCNA, N-cadherin, p-MAPK/MAPK, p-ERK1/2/ERK1/2, S-phase cell proportion, and levels of c-Fos and c-Jun (P<0.05); apoptosis rate, E-cadherin, Cleaved-CASP9 protein levels, and G0/G1-phase cell proportion were increased (P<0.05). Compared with the 200 nmol/L remifentanil group, the remifentanil+C16-PAF group showed partial reversal of these trends in AGS cells (P<0.05). In summary, remifentanil can inhibit malignant biological behaviors of esophagogastric junction adenocarcinoma cells by suppressing the MAPK/ERK pathway.

CSTR: 32200.14.cjcb.2025.12.0008