摘要
目的探讨Bortezomib对非小细胞肺癌(NSCLC)细胞周期、增殖、凋亡及核转录因子(NF-κB)的影响。方法采用MTT法检测Bortezomib对细胞生长的抑制作用,流式细胞仪分析Bortezomib对细胞周期及凋亡的影响,Western blotting检测Borte-zomib对NF-κB、IκB和Bcl-2表达的影响。结果随着作用时间和药物浓度的增加,Bortezomib对NSCLC细胞的生长抑制作用越明显。25nmol/L的Bortezomib作用48h可以使细胞周期阻滞在G2/M期。6种NSCLC细胞中均有NF-κB的基础性表达,且胞核中NF-κB的表达水平与胞质IκB的表达水平呈反比。Bortezomib对细胞中NF-κB的基础表达水平没有影响,但能明显抑制TNF-α诱导的NF-κB的核转位,并下调抗凋亡蛋白Bcl-2的水平,且这种抑制作用呈时间和剂量依赖趋势。结论Bortezomib能够抑制NSCLC细胞增殖,并诱导凋亡发生,可能是通过NF-κB通路发挥作用。
Objective To study the effect of Bortezomib on proliferation, apoptosis, cell cycles and activation of NF-κB of non-small cell lung cancer cells （NSCLC） in vitro. Methods The inhibitory action of Bortezomib on cellular growth was determined by MTT. The effects of Bortezomib on cell cycle and apoptosis were assessed by flow cytometry. The influence of Bortezomib on the expressions of NF-κB, IκB and Bcl-2 were detected with Western blotting. Results The inhibitory effects of Bortezomib on the proliferation of NSCLC cells showed a time-and concentration-dependent manner. The growth of NSCLC cells was arrested at G2/M stage after treatment with Bortesomib at 25nmol/L for 48h. Basal expression of NF-κB was found to exist in all the 6 cell lines, with NF-κB expression in nucleus showing an inverse correlation with IκB expression in cytoplasm. Bortezomib threw no significant influence on the basal expression of NF-κB, but significantly blocked the TNF-α-induced nuclear translocation of NF-κB and down-regulated the expression of anti-apoptosis protein Bcl-2 in a time-and concentration-dependent manner. Conclusion With NF-κB-dependent pathway, Bortezomib may inhibit the proliferation of NSCLC cells and induce apoptosis.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2010年第5期568-572,共5页
Medical Journal of Chinese People's Liberation Army
