摘要Background Tumor hypoxia,one of the features of solid tumors,is associated with chemo-resistance.Recently,nuclear factor-KB (NF-kB) was found to be activated during hypoxia.However,the impact of NF-kB activation on chemo-resistance during hypoxia remains unknown.Methods Human lung adenocarcinoma A549 cells were transfected with NF-kB p65siRNA and treated with cobalt chloride (CoCl2) to mimic hypoxia in the presence or absence of cisplatin.NF-kB expression was measured by Western blotting,immune-fluorescence and real-time PCR.Hypoxia-inducible factor-1α (HIF-1α) and Bcl-2 expression were determined by Western blotting.Cell apoptosis and survival with half-maximum inhibitory concentration (IC50) of cisplatin were determined by Annexin V-FITC/PI and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT),respectively.Results Exposure ofA549 cells to CoCl2 increased nuclear HIF-1α protein expression,and enhanced NF-kB p65 protein nuclear accumulation (the mark of NF-kB activation) in a time and dose dependant manner.CoCl2 did not promote apoptosis in A549 cells; on the contrary,it reduced cisplatin-induced apoptosis and increased the IC50 of cisplatin.However,when we inhibited CoCl2-induced activation of NF-kB through NF-kB p65siRNA,cisplatin-induced apoptosis was increased and IC50 of cisplatin was reduced to levels similar to those in control cells.Meanwhile,CoCl2-induced Bcl-2 overexpression was down-regulated in the presence of cisplatin when NF-KB activity was inhibited.Conclusion Up-regulating Bcl-2 might be involved in NF-kB activation induced resistance to cisplatin in A549 cells under CoCl2-induced chemical hypoxia.