Gefitinib Induces Apoptosis of Gastric Cancer Cells by Promoting Glutaminolysis Through the MEK/ERK Signaling Pathway

Abstract

We aimed to investigate the effect of gefitinib on the proliferation and apoptosis of gastric cancer (GC) cells through the MEK/ERK signaling pathway. The GC cell line NCI-N87 was cultured in vitro and divided into a control group and a gefitinib group. Cell viability for NCI-N87 was determined using the MTT test. The amount of apoptosis in NCI-N87 cells was measured using flow cytometry. Real-time quantitative PCR was used to measure GDH1 mRNA expression in NCI-N87 cells. P-MEK1/2, MEK1/2, P-ERK1/2, and ERK1/2 protein expression levels in NCI-N87 cells were determined using Western blotting. An assay kit for measuring glutamine was used to determine the intracellular glutamine concentration of NCI-N87 cells. The proliferative activity of NCI-N87 cells was significantly inhibited in the gefitinib group compared to the control group, along with the transcription level of GDH1, intracellular glutamine content, intracellular glutamine content reduction, and p-MEK1/2 and p-ERK1/2 protein expression levels. Gefitinib inhibits proliferation and promotes apoptosis in the GC cell line NCI-N87 by downregulating the EGFR/MEK/ERK signaling pathway. Mechanistically, it is achieved by promoting the expression of GDH1 to promote glutaminolysis in NCI-N87 cells.