南方医科大学学报2018，Vol.38Issue(5)：584-590,7.
NF-κB亚单位p50/p65激活促进肺腺癌H1650细胞吉非替尼耐药
Activation of nuclear factor-κB subunit p50/p65 enhances gefitinib resistance of lung adenocarcinoma H1650 cell line
摘要
Abstract
Objective To explore the intrinsic connection between activation of classical nuclear factor-κB(NF-κB)pathway and gefitinib resistance in human lung adenocarcinoma H1650 cells. Methods Human lung adenocarcinoma H1650 cells were exposed to gefitinib continuously for 60 days to obtain resistant H1650 cells.The expressions of P-IκBα,P-p50 and P-p65 in the cytoplasm or nuclei were detected using Western blotting in human lung adenocarcinoma HCC827 cells,parental H1650 cells and gefitinib-resistant H1650 cells. The effects of gefitinib alone or in combination with PDTC on the survival rate and expressions of NF-κB P-p50 and P-p65 were compared among the 3 cell lines.Results Gefitinib-resistant H1650 cells showed increased cytoplasmic and nuclear P-IκBα expressions.The expressions of P-p50 and P-p65 differed significantly among the 3 cell line,decreasing in the order of resistant H1650 cells,parental H1650 cells,and gefitinib sensitive HCC827 cell lines(P<0.05 or 0.01).Treatment with gefitinib alone resulted in a significantly lower cell inhibition rate in resistant H1650 cells than in the parental H1650 cells (P<0.05) and HCC827 cells (P<0.01). The resistant H1650 cells had a significantly higher expression of P-p50 and P-p65 than other two cell lines(P<0.05).In both the resistant and parental H1650 cells,gefitinib significantly lowered P-p50 and P-p65 expressions(P<0.05 or 0.01),and the combined treatment with gefitinib and PDTC significantly decreased the cell survival rate and further lowered the cytoplasmic and nuclear expressions of P-p50 and P-p65(P<0.01 or 0.01).Conclusion The activation of classical NF-κB pathway is a key factor contributing to transformation of the parental H1650 cells into gefitinib-resistant cells.Gefitinib combined with PDTC can inhibit P-IκBα production and NF-κB P-p50 and P-p65 activation to suppress the survival of residual H1650 cells and the generation of gefitinib-resistant cells.关键词
肺腺癌/活化的B细胞核因子κ-轻链增强子/磷酸化p50和p65/H1650细胞株/吡咯烷二硫代氨基甲酸盐Key words
lung adenocarcinoma/nuclear factor kappa-light chain enhancer of activated B cells/Phospho-p50 and Phospho-p65/H1650 cell line/pyrrolidine dithiocarbamate salt引用本文复制引用
潘莹,张楠,全文,黄思超,王霞,龚五星,梁翠微,杜均祥,彭东旭,谢云,郑礼平..NF-κB亚单位p50/p65激活促进肺腺癌H1650细胞吉非替尼耐药[J].南方医科大学学报,2018,38(5):584-590,7.基金项目
珠海市科技计划医疗卫生项目(一般项目)(20161027E030026) （一般项目）
