Silencing of syndecan-binding protein enhances the inhibitory effect of tamoxifen and increases cellular sensitivity to estrogen.

Silencing of syndecan-binding protein enhances the inhibitory effect of tamoxifen and increases cellular sensitivity to estrogen.
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沉默多聚糖结合蛋白可增强他莫昔芬的抑制作用并增加细胞对雌激素的敏感性

DOI:
10.20892/j.issn.2095-3941.2017.0122
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发表时间:
2018-03
影响因子:
5.5
通讯作者:
Fu L
Fu L
中科院分区:
医学2区
文献类型:
--
作者:
Zhang J;Qian X;Liu F;Guo X;Gu F;Fu L

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目的:他莫昔芬被用作雌激素受体(ER)阳性乳腺癌(BCa)的补充治疗,但许多患者产生了耐药性。本研究的目的是探讨多配体聚糖结合蛋白 (SDCBP) 沉默在 ER 阳性 BCa 细胞中的作用。方法:在 MCF-7/T47D 细胞中,检测 SDCBP 沉默/过表达对细胞增殖和雌激素反应的影响。使用 MTT 测定检查细胞增殖,并通过蛋白质印迹检查细胞周期调节剂。通过荧光素酶活性和雌激素施用后 pS2 和孕酮受体 (PR) 转录水平的评估来检查雌激素反应。用ERα、PR和SDCBP抗体对ER阳性BCa样本进行染色,并分析它们的表达相关性。结果:我们发现,与单独使用他莫昔芬相比,SDCBP 沉默可抑制 ER 阳性 BCa 细胞的增殖,并将更多细胞停滞在细胞周期的 G1 期,而 SDCBP 过度表达限制了他莫昔芬的抗癌作用。 SDCBP 沉默和过度表达也分别增强和减弱雌激素反应。 ER阳性BCa组织样本中SDCBP的表达与PR、ERα以及PR/ERα比值呈负相关。结论:SDCBP 可能参与 ER 阳性 BCa 的他莫昔芬耐药。他莫昔芬治疗联合 SDCBP 沉默可能为内分泌治疗耐药的 BCa 提供一种新的治疗方法。
Objective: Tamoxifen is used as a complementary treatment for estrogen receptor (ER)-positive breast cancer (BCa), but many patients developed resistance. The aim of this study was to examine the role of syndecan-binding protein (SDCBP) silencing in ER-positive BCa cells. Methods: In MCF-7/T47D cells, the effects of SDCBP silence/overexpression on cell proliferation and estrogenic response were examined. Cell proliferation was examined using the MTT assay and cell cycle regulators were examined by Western blot. Estrogen response was examined from a luciferase activity and evaluation of transcript levels of pS2 and progesterone receptor (PR) upon estrogen administration. Samples of ER-positive BCa were stained with ERα, PR, and SDCBP antibodies, and their expression correlations were analyzed. Results: We found that SDCBP silencing inhibited the proliferation of ER-positive BCa cells and arrested a greater number of cells in the G1 phase of the cell cycle compared to tamoxifen alone, while SDCBP overexpression limited the anti-cancer effects of tamoxifen. SDCBP silencing and overexpression also enhanced and attenuated the estrogenic response, respectively. Expression of SDCBP was negatively correlated with PR, ERα, and the PR/ERα ratio in ER-positive BCa tissue samples. Conclusions: SDCBP may be involved in tamoxifen resistance in ER-positive BCa. Tamoxifen treatment combined with SDCBP silencing may provide a novel treatment for endocrine therapy-resistant BCa.
DOI: 10.1023/a:1025484908380
发表时间: 2003-09-01
影响因子: 3.8
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影响因子: 14.9
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DOI: 10.1371/journal.pone.0171169
发表时间: 2017
期刊: PloS one
影响因子: 3.7
作者:
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通讯作者: Fu L