在人乳腺癌细胞增殖中LXRα、NF-κB p65和cyclinD1的差异表达

Different Expression of LXRα,NF-κB p65 and Cyclin D1 in The Proliferation of Human Breast Cancer Cells

ES评分 0

DOI
刊名
年,卷(期) 2016, 43(03)
作者
作者单位 1.南华大学药物药理研究所2.南华大学第一附属医院

摘要
LXRα可以抑制包括乳腺癌在内的多种肿瘤细胞的增殖,而这种抑制作用的具体机制尚不明了.因此本文探讨了LXRα、NF-κB p65和cyclin D1三者在人乳腺癌细胞增殖中的差异表达.首先采用免疫组化法检测了乳腺癌及癌旁组织中LXRα,NF-κB p65和cyclin D1的表达,结果表明,3种蛋白主要表达于细胞核,且NF-κB p65和cyclin D1在癌组织中的表达显著高于癌旁组织,而LXRα则在癌组织中表达显著降低.用MTT和Western blot检测TO901317对乳腺癌细胞增殖及3种蛋白表达的影响,结果显示,随着TO901317浓度的增加与时间的延长,其对细胞增殖的抑制作用逐渐增强,与此同时能上调LXRα的表达,并下调NF-κB p65和cyclin D1的表达.进一步通过RNA干扰技术下调LXRα的表达,以及应用NF-κB抑制剂PDTC观察TO901317上述作用的改变,发现LXRαsiR NA显著降低TO901317对3种蛋白表达的影响和对细胞增殖的抑制作用.而PDTC则加强TO901317的上述作用效果,除了几乎不影响LXRα的表达外.综上所述,LXRα/NF-κB p65/cyclin D1在乳腺癌细胞增殖中具有重要作用,有助于进一步明确LXRα为新的乳腺癌调控靶点,为今后乳腺癌的分子靶向治疗提供新的思路.
Abstract
LXRα could have the anti-proliferative effect on multiple cancer cells including breast cancer.However,the mechanisms of LXRα regulating the breast cancer cells remain unclear.This study is to investigate the different expression of LXRα,NF-κB p65 and cyclin D1 in the proliferation of human breast cancer cells.At first,LXRα,NF-κB p65 and cyclin D1 expression were detected by immunohistochemical staining in human breast cancer and paired adjacent breast tissues(n=60).As a result,the three kinds of protein were mainly expressed in cell nuclei.Among them,NF-κB p65 and cyclin D1 were higher expressed in breast cancer tissues than in adjacent tissues while LXRα was lower expressed.Then,MTT assay was used to detect the proliferation of MCF-7 cells and Western blot was used to examine the expression of the three kinds of protein.TO901317(a kind of artificial agonists against LXRs especially for LXRα)could increase LXRα expression,but decrease NF-κB p65 and cyclin D1 expression and suppress the proliferation of MCF-7cells in a dose-and time-dependent manner(P<0.05).Finally,the effects of LXRα siR NA and pyrrolidinedithiocarbamic acid(PDTC,an inhibitory of NF-κB)on TO901317 were observed respectively.LXRα siR NA could significantly decrease the up-regulation of LXRα expression and reverse the inhibited effect of TO901317 on cyclin D1 and NF-κB p65 expression and MCF-7 cell proliferation(P<0.05)while PDTC could strengthen the inhibition of cell proliferation and further down-regulate NF-κB p65 and cyclin D1 expression induced by TO901317(P<0.05),but have little effect on LXRα.In a conclusion,the expression of LXRα,NF-κB p65 and cyclin D1 plays an important role in the proliferation of human breast cancer cells,so as to provide a new method for the molecular targeting treatment of breast cancer in the future.
关键词
肝X受体α,核因子-κB,p65周期蛋白D1,细胞增殖,TO901317
KeyWord
LXRα, NF-κB p65, cyclinD1, cell proliferation, TO901317
基金项目
页码 226-235
  • 参考文献
  • 相关文献
  • 引用本文

涂剑刘晓旺李涛余平丁维珂陆凯强陈霄霄彭露周志刚. 在人乳腺癌细胞增殖中LXRα、NF-κB p65和cyclinD1的差异表达 [J]. 生物化学与生物物理进展. 2016; 43; (03). 226 - 235.

  • 文献评论

相关学者

相关机构