EGF Induced CXCR4 Expression in NSCLC Cell Through PI-3K Signaling Pathway

Objective: To study the relationship between EGFR and CXCR4 in non-small cell lung cancer cell line A549.Methods: Serum-starved A549 cells were stimulated with different concentration of EGF(20 μg/L,40 μg/L,and 60 μg/L) for 24 hours and then CXCR4 expression levels were evaluated by real time PCR.Serum starved A549 cells were treated with AG1478(specific inhibitor of EGFR phosphorylation)(10 μmol/L) for 24 h,CXCR4 expression were re-evaluated by real-time PCR and Western blot.Serum-starved A549 cells were treated with EGF in the presence or absence of LY294002(PI-3 kinase pathway inhibitor) to investigate the changes of CXCR4 mRNA levels.Results: EGF up-regulated CXCR4 expression about 3 to 4 folds.CXCR4 expression was reduced after treatment with EGFR phosphorylation inhibitor(AG1478).EGF induced up-regulation of CXCR4 is enhanced through PI-3 kinase pathway,and CXCR4 mRNA up-regulation increased in a concentration-dependant manner.Conclusion: EGF up-regulates the CXCR4 expression through PI-3K signaling pathway,and this interaction between CXCR4 and EGFR intracellular signaling pathways may contribute to tumor progression.Inhibition of both EGFR and CXCR4 may be potential therapeutic targets for NSCLC patients who have concomitant over expression of CXCR4 and EGFR.