Knockdown of GluA2 induces apoptosis in non-small-cell lung cancer A549 cells through the p53 signaling pathway.

Abstract

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are important glutamatergic receptors that mediate fast excitatory synaptic transmission in the brain. Previous studies have demonstrated that glutamate ionotropic receptor AMPA type subunit 2 (GluA2), one of the four subunits that comprise AMPA receptors, is a potential novel marker for poor prognosis in patients with human lung cancer. However, the mechanisms of GluA2-induced apoptosis, proliferation and migration in lung cancer remain unknown. The present study aimed to explore the mechanisms underlying these effects of GluA2 in human lung cancer by silencing GluA2 in A549 cells. Using the Cell Counting Kit-8 assay, western blot analysis and acridine orange/ethidium bromide staining, downregulation of GluA2 was revealed to significantly inhibit the proliferation and significantly promote the apoptosis of A549 cells. Knockdown of GluA2 was also revealed to be associated with increased caspase-3 activity, increased Bcl-2-associated X protein and Bcl-2-associated death promoter (Bad) expression, and decreased expression of B-cell lymphoma-2, p-Bad and X-linked inhibitor of apoptosis protein. In addition, GluA2 silencing upregulated cellular tumor antigen p53 (p53)/p21Cip1/Waf1/p16INK4a protein. In conclusion, these results indicate that the effects of GluA2 in lung cancer are mediated by the caspase-3 and p53/p21Cip1/Waf1/p16INK4a signaling pathways. Therefore, GluA2 may be a potential novel therapeutic target for the treatment of lung cancer.