Inhibition of nuclear factor-κB activity enhanced chemosensitivity to cisplatin in human

Inhibition of nuclear factor-κB activity enhanced chemosensitivity to cisplatin in human lung adeno-carcinoma A549 cells under chemical hypoxia

conditions

LI Fang;HUANG Li;SU Xiao-li;GU Qi-hua;HU Cheng-ping

【期刊名称】《中华医学杂志（英文版）》 【年(卷),期】2013(126)017

【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