Abstract： Objective To study the effect of morphine on proliferation and apoptosis of human nasopharyngeal carcinoma cell line CNE-2 and the possible mechanism. Methods CNE-2 cells were treated with culture medium containing different concentrations of morphine(0.1,1,10,100 and 1000 mg/L) in study groups or with the same volume culture medium in control group. The inhibition rate of cell proliferation was measured by MTT assay after the CNE-2 cells were incubated with morphine for 24,48 h and 72 h. At 48hours after treatment with different concentrations of morphine,apoptosis of CNE-2 cells was assessed by Hoechst33258 fluorescence stained and flow cytometry (FCM),the protein levels of Bcl-2,Bax,caspase-3and cleaved-caspase-3 were measured by Western blotting. Results At all the time-spots,treatment with morphine at concentrations ranging from 0.1 to 100 mg/L was not shown to interfere with proliferation of CNE-2 cells. However,growth inhibition was observed with 1000 mg/L morphine,which appeared more intense along with time[(15.0±4.4)% at 24 h,(30.7±4.9)% at 48 h and(50.0±4.4) at 72 h]. At 48 hours,fluorescence microscopy showed that apoptosis of CNE-2 was not present in the control group,modest in 0.1-100 mg/L morphine treated groups,and typical in a great percentage of cells in 1000 mg/L morphine treated group. FCM showed that the apoptosis rate in 0.1-100 mg/L morphine treated groups did not differ significantly from the control group,but was remarkably increased in the 1000 mg/L morphine treated group as compared with the control group[(39.33±6.03)% vs (9.36± 1.57)%,P<0.05]. By Western blotting,treatment with 1000 mg/L morphine was shown to result in inhibited Bcl-2 expression,increased Bax expression,induced caspase-3 activation and enhanced cleaved-caspase-3 production,whereas these were not observed with 0.1,1,10,100 mg/L morphine,as compared with the control group. Conclusion Highdose morphine may induce apoptosis of human nasopharyngeal carcinoma cell line CNE-2 by the downregulation of Bcl-2,up-regulation of Bax that together leads to activation of caspase-3.