2016年第43卷第3期目录
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封面故事:乳腺癌是女性常见的恶性肿瘤,涂剑、刘晓旺和周志刚课题组通过收集的多例临床标本发现,与炎症调控密切关联的孤儿核受体成员肝X受体α (LXRα) 在乳腺癌组织核内表达显著降低,而连接炎-癌转变的另一关键分子核转录因子(NF-κB p65) 表达明显增高.运用LXRs激动剂TO901317进一步发现,TO901317呈浓度和时间依赖性上调LXRα、下调 NF-κB p65表达,明显抑制乳腺癌细胞增殖;LXRα siRNA可显著延缓TO901317的上述作用,NF-κB抑制剂PDTC则可加强TO901317的这一效果.上述结果有利地支持LXRα作为抑癌基因,成为乳腺癌调控的新靶点,证实炎症相关的信号通路将成为抗肿瘤治疗的重要靶点,有望为乳腺癌的分子靶向治疗和“炎-癌”转变分子机制研究提供新的思路.
(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,本期第226~235页)
Cover Story: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 cyclinD1 in the proliferation of human breast cancer cells. At first, LXRα, NF-κB p65 and cyclinD1 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 cyclinD1 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 cyclinD1 expression and suppress the proliferation of MCF-7 cells in a dose- and time-dependent manner (P < 0.05). Finally, the effects of LXRα siRNA and pyrrolidinedithiocarbamic acid (PDTC, an inhibitory of NF-κB) on TO901317 were observed respectively. LXRα siRNA could significantly decrease the up-regulation of LXRα expression and reverse the inhibited effect of TO901317 on cyclinD1 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 cyclinD1 expression induced by TO901317 (P < 0.05), but have little effect on LXRα. In a conclusion, the expression of LXRα, NF-κB p65 and cyclinD1 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.
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综述与专论
研究报告
技术与方法
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