ITE, an endogenous aryl hydrocarbon receptor ligand, suppresses endometrial cancer cell proliferation and migration
ITE, an endogenous aryl hydrocarbon receptor ligand, suppresses endometrial cancer cell proliferation and migration
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ITE 是一种内源性芳烃受体配体，可抑制子宫内膜癌细胞增殖和迁移
DOI：
10.1016/j.tox.2019.03.017
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发表时间：
2019-06-01
期刊：
影响因子：
4.5
通讯作者：
Wan Xiaoping
中科院分区：
文献类型：
--
作者：
Bian Yiding;Li Yiran;Wan Xiaoping
背景：寻找新的分子靶点治疗子宫内膜癌（EC）是一个重要的临床目标，特别是对于那些对常规治疗产生耐药性的患者。芳烃受体（AhR）是一种配体激活的转录因子，主要被认为是二恶英毒性的中介。然而，AhR也能以配体依赖的方式抑制细胞增殖，并在小鼠中作为肿瘤抑制因子，因此可能是一个潜在的抗癌靶点。在本研究中，我们研究了内源性AhR配体2-（1' h -吲哚-3'-羰基）-噻唑-4-羧酸甲酯（ITE）是否通过AhR调节EC细胞的增殖和迁移。方法：采用实时荧光定量PCR和western blot检测AhR在EC组织及配对的邻近正常组织中的表达。此外，我们还进行了transwell实验，以测试ITE处理是否改变了EC细胞的运动电位和增殖。接下来，我们建立了小鼠异种移植模型，进一步探索ITE在体内的作用。结果：我们发现EC组织中AhR蛋白和RNA水平相对于癌旁正常子宫内膜组织有轻度升高。此外，ITE还能抑制体外EC细胞的增殖和迁移，并抑制小鼠EC细胞的异种移植物生长。结论：我们的结果强烈支持使用ITE作为小分子化合物治疗EC的可能性。
Background: Identification of new molecular targets for the treatment of endometrial cancer (EC) is an important clinical goal, especially for the patients which were resistant to conventional therapies. The aryl hydrocarbon receptor (AhR) is a ligand- activated transcription factor known primarily as the mediator of dioxin toxicity. However, the AhR can also inhibit cellular proliferation in a ligand-dependent manner and act as a tumor suppressor in mice, thus may be a potential anticancer target. In this study, we investigated if the endogenous AhR ligand 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) regulated proliferation and migration of EC cells via AhR.Methods: We used quantitative real-time PCR and western blot to assess the expression of AhR in EC tissues and paired adjacent normal tissues. In addition, we conducted transwell assay to test whether the treatment of ITE altered the locomotive potential and proliferation of EC cells. Next, we conducted mouse xenograft models to further explore the in vivo effect of ITE.Results: We found that the AhR protein and RNA levels were increased mildly in EC tissues relative to the para-tumor normal endometrial tissues. Besides, ITE suppressed EC cells proliferation and migration in vitro, and also suppressed EC cells xenograft growth in mice.Conclusions: Our results strongly supported the possibility of using the ITE as a small molecular compound for the treatment of EC.