The Function Of NMDA Receptor In Non-small Cell Lung Cancer Cell Lines

Lung cancer is a leading cause of death from cancer.Non-small cell lung cancer is recognized as one of the most malignant human cancers.Because the origin and progression of non-small cell lung cancer(NSCLC)is still unclear,the treatment of this disease has progressed very slowly.Previous studies have found that large amounts of glutamate are commonly released in tumor tissue.In addition,it has been found that NMDA receptors are expressed in a variety of cancer cells,so the secretory/paracrine release of glutamate may act as extracellular stimulus to activate N-methyl-D-aspartic acid(NMDA)receptors in cancer cells,thus promoting the aggressive growth of tumors.However,the expression,subunit specific function and physiological significance of different subtypes of NMDA receptors in non-small cell lung cancer cells are not very clear.First,we analyzed the expression of NMDA receptor subunits Grin1 and Grin2 B in non-small cell lung cancer through the Gene Expression Omnibus(GEO)public database,and found that the expression of Grin1 and Grin2B in non-small cell lung cancer tumors was significantly increased compared with normal tissues.Then We found NMDA receptors in non-small cell lung cancer cells A549,NCL-H1299 and NCL-H460 by reverse transcription PCR and western blot.The existence of functional NMDA receptors in non-small cell lung cancer cells was revealed by cytoimmunochemical and electrophysiological methods.According to the results of Cell Counting Kit-8 experiments,plate cloning experiments and apoptosis kits,specific inhibition of GluN2 B subunit of NMDA receptor can inhibit the activity and migration of non-small cell lung cancer cells,and promote the apoptosis of non-small cell lung cancer cells.Xenograft studies have demonstrated that specific inhibitors of the GluN2 B subunit of the NMDA receptor can delay tumor development.Our findings suggest that the GluN2 B subunit of NMDA receptor is very important for the proliferation,migration and apoptosis of non-small cell lung cancer cells,and it is expected to be a biomarker and potential molecular target for the treatment of NSCLC,which may help prolong the survival of patients with non-small cell lung cancer clinically.