[1]皮玉瑞,李同辉,陈秀彬,等.前列腺癌细胞中多烯紫杉醇下调Smad3不依赖TGF-β1信号[J].南京师范大学学报(自然科学版),2016,39(03):89.[doi:10.3969/j.issn.1001-4616.2016.03.015]
　Pi Yurui,Li Tonghui,Chen Xiubin,et al.Docetaxel Down-Regulation of Smad3 Expression in Prostate CancerCell Lines Independent of TGF-β1 Signaling[J].Journal of Nanjing Normal University(Natural Science Edition),2016,39(03):89.[doi:10.3969/j.issn.1001-4616.2016.03.015]
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前列腺癌细胞中多烯紫杉醇下调Smad3不依赖TGF-β1信号()
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《南京师范大学学报》（自然科学版）[ISSN:1001-4616/CN:32-1239/N]

卷:
第39卷
期数:
2016年03期
页码:
89
栏目:
·生命科学·
出版日期:
2016-09-30

文章信息/Info

Title:
Docetaxel Down-Regulation of Smad3 Expression in Prostate CancerCell Lines Independent of TGF-β1 Signaling
文章编号:
1001-4616（2016）03-0089-07
作者:
皮玉瑞; 李同辉; 陈秀彬; 刘　平; 卢　山
南京师范大学生命科学学院，江苏省分子医学生物技术重点实验室，江苏 南京 210023
Author(s):
Pi Yurui; Li Tonghui; Chen Xiubin; Liu Ping; Lu Shan
School of Life Sciences，Nanjing Normal University，Jiangsu Key Laboratory for Molecular and Medical Biotechnology，Nanjing 210023，China
关键词:
多烯紫杉醇; Smad3; 前列腺癌; 下调
Keywords:
docetaxel; Smad3; prostate cancer; down-regulation
分类号:
Q28
DOI:
10.3969/j.issn.1001-4616.2016.03.015
文献标志码:
A
摘要:
多烯紫杉醇（Docetaxel，DOC）来源于欧洲红豆杉针叶，作为紫杉烷类抗癌药物，已被广泛应用于多种癌症临床治疗中，但相关机理还有很多不清楚的地方. 本研究主要通过逆转录聚合酶链式反应（RT-PCR）和蛋白免疫印迹实验（Western blot）等方法观察有TGF-b信号存在的前列腺癌细胞PC-3中DOC对Smad3表达水平的调控作用，再利用TGF-b RII缺失的前列腺癌细胞LNCaP来探讨不依赖TGF-b1信号时DOC对细胞生长、Smad3表达的影响及其分子机制. 结果发现DOC不仅能以时间和浓度依赖方式下调PC-3细胞中Smad3的mRNA和蛋白表达水平，也能在LNCaP细胞中选择性地降低Smad3表达水平和抑制细胞生长，还能减少几乎不含TGF-b1的PC-3细胞中Smad3表达水平. 同时，两种细胞中Stat1表达水平均受到DOC显著抑制，而且，Stat1和Smad3能相互结合形成复合体. 进一步分析Smad3核心启动子区域也预测存在5个Stat1结合位点. 这些结果说明DOC下调Smad3不依赖于TGF-b1信号通路，且可能是通过调控Stat1在Smad3启动子内的结合来作用.
Abstract:
As a taxane anticancer drug，docetaxel（DOC）derived from the European yew needles has been widely used as the therapies for multiple cancers in clinic though a lot of related mechanism remains unclear. In this study，the DOC regulation of Smad3 expression in the presence of TGF-b signal was first observed in prostate cancer cell line PC-3 level，and then the effects of DOC on cell growth and Smad3 expression in the absence of TGF-b1 signal was investigated in prostate cancer LNCaP cells without TGF-b RII to explore related mechanism mainly by reverse transcription polymerase chain reaction（RT-PCR），Western blot，etc. It was found that DOC not only down-regulated Smad3 mRNA and protein levels in PC-3 cells in a time-and dose-dependent ways，but also selectively reduced Smad3 expression and inhibited cell growth in LNCaP cells while Smad2 expression was not decreased，and DOC also reduced Smad3 expression in PC-3 cells cultured in the absence of TGF-b1. Meanwhile，the Stat1 expressions in both of PC-3 and LNCaP cells were significantly inhibited by DOC. Moreover，Stat1 and Smad3 could bind together to form complex. Besides，it is also speculated that 5 potential binding sites for Stat1 existed from the analysis for Smad3 core promoter region. In total，DOC down-regulation of Smad3 is not depend on the TGF-b1 signaling，and may be caused by affecting Stat1 bindings with Smad3 promoter specific sites.

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备注/Memo

备注/Memo:
收稿日期：2016-02-28.　
基金项目：国家自然科学基金（81172007、81272850）.　
通讯联系人：卢山，教授，硕士生导师，研究方向：肿瘤发生发展分子机理及调控. E-mail：lu_shan@hotmail.com
更新日期/Last Update: 2016-09-30