Notch 1 signaling is active in ovarian cancer
Notch 1 signaling is active in ovarian cancer
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DOI：
10.1016/j.ygyno.2009.12.003
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发表时间：
2010-04-01
影响因子：
4.7
通讯作者：
Seiler, Nicole
中科院分区：
文献类型：
--
作者：
Rose, Stephen L.;Kunnimalaiyaan, Muthusamy;Seiler, Nicole
客观的。尽管化疗和根治性手术取得了进展，但大多数晚期卵巢癌患者死于疾病，这凸显了开发新治疗策略的必要性。 Notch信号通路在细胞分化、增殖和凋亡中发挥重要作用。我们假设 Notch 1 的活性形式，即 Notch 1 胞内结构域 (NICD)，将在卵巢癌细胞中过度表达，并且 NICD 的消耗将导致生长减少。方法。经机构审查委员会批准后，对人类卵巢癌标本以及卵巢癌细胞系 OVCAR3 中的 NICD 表达进行了分析。 SKOV3 和 CaOV3。此外，在用针对Notch 1的siRNA转染后6天，通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑(mu)生长测定检测Notch 1耗尽对卵巢癌细胞生长的影响。结果。蛋白质印迹分析显示，所有 3 种卵巢癌细胞系以及 21 个人类卵巢癌样本中的 16 个 (76%) 都有丰富的 NICD 表达。用 Notch 1 siRNA 处理后，所有三种细胞系中 NICD 的表达均大大降低。此外，NICD 的这种消耗与所有三种卵巢癌细胞系的显着生长抑制相关。结论。 NICD 在卵巢癌细胞系和人类卵巢癌标本中频繁表达。重要的是，Notch 1 的缺失导致卵巢癌细胞的生长受到抑制。这些发现支持了 Notch 1 在卵巢癌增殖中发挥作用的假设，鼓励将该通路作为治疗靶点进行研究。 (C) 2009 Elsevier Inc. 保留所有权利。
Objective. Despite advances in chemotherapy and radical surgery, most advanced stage ovarian cancer patients die from their disease, highlighting the need for the development of novel treatment strategies. The Notch signaling pathway plays an important role in cellular differentiation, proliferation and apoptosis. We hypothesized that the active form of Notch 1, the Notch 1 intracellular domain (NICD), would be overexpressed in ovarian cancer cells and that depletion of NICD would lead to growth reduction.Methods. Following institutional review board approval, NICD expression was analyzed in human ovarian cancer specimens as well as the ovarian cancer cell lines OVCAR3. SKOV3, and CaOV3. In addition, the effects of Notch 1 depletion on ovarian cancer cell growth were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (mu) growth assay for 6 days following transfection with siRNA against Notch 1.Results. Western blot analysis revealed abundant NICD expression in all 3 ovarian cancer cell lines, as well as in 16 of 21 (76%) human ovarian cancer samples. Following treatment with Notch 1 siRNA, expression of NICD was greatly reduced in all three cell lines. Furthermore, this depletion of NICD was associated with significant growth inhibition of all three ovarian cancer cell lines.Conclusions. NICD was frequently expressed in ovarian cancer cell lines and human ovarian cancer specimens. Importantly, depletion of Notch 1 led to growth inhibition of ovarian cancer cells. These findings support the hypothesis that Notch 1 plays a role in ovarian cancer proliferation, encouraging the investigation of this pathway as a therapeutic target. (C) 2009 Elsevier Inc. All rights reserved.