Objective:To investigate the effect and mechanism of anesthetic ketamine and morphine on the proliferation of cultured human lung adenocarcinoma A549 cell. Methods:Human lung adenocarcinoma A549 cells were treated with different concentration of ketamine(K1,K2,K3 is 100,200,and 400 μg/mL,respectively)and morphine(M1,M2,M3 is 25,50 and 100 μg/mL,respectively)for 24 and 48 h. After cultured for 24 h,the effect of ketamine and morphine on the invasive ability of A549 cells were measured by transwell invasion. NF-κB transcription activity were determined by luciferase assay. After cultured for 48 h,the proliferation inhibition rates of A549 cells were assessed by methyl thiazolyl tetrazolium (MTT) assay. Protein expressions of NF-κB P65 were determined by Western blot. IL-1β and COX-2 expression were determined by QPCR. Results:(1)Compared with the control group,M1 and M2 enhanced A549 cell proliferation and migration (P < 0.05),while K1,K2 and K3 suppressed A549 cells migration(P < 0.05). (2)M1,M2 and M3 enhanced IL-1β and COX-2 expression(P < 0.05),but K2 and K3 had opposing effects(P < 0.05). M1,M2,and M3 enhanced NF-κB and P65 transcription activity and protein expressions(P < 0.05),while K1,K2 and K3 had opposing effects(P < 0.05). Conclusion:Unlike opioids,ketamine inhibits the proliferation and migration of A549 through NF-κB and its down stream factor IL-1β and COX-2,may be more suitable for lung cancer patients postoperative analgesia.