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催产素通过上调早期生长反应因子-1抑制头颈部鳞状细胞癌细胞迁移。

Oxytocin inhibits head and neck squamous cell carcinoma cell migration by early growth response-1 upregulation.

作者信息

Kim Jinkyung, Kang Sung-Min, Lee Heon-Jin, Choi So-Young, Hong Su-Hyung

机构信息

Departments of aOral Microbiology and Immunology bOral and Maxillofacial Surgery, School of Dentistry, Kyungpook National University, Daegu, South Korea.

出版信息

Anticancer Drugs. 2017 Jul;28(6):613-622. doi: 10.1097/CAD.0000000000000501.

Abstract

The effect of oxytocin (OXT) on cancer invasion is controversial. Few studies have examined the effect of early growth response-1 (EGR1) on the invasion of head and neck squamous cell carcinoma (HNSCC). Here, we evaluated how EGR1 affects HNSCC cell migration through the molecular mechanism of OXT in exerting anti-invasion activity. Matrigel invasion and wound-healing assays were used to measure the in-vitro cell migration. The molecular mechanism of OXT was assessed by knockdown or overexpression of EGR1 in HNSCC cells. Three-dimensional (3-D) spheroids formation, followed by the image analysis for quantification was performed. OXT at 500 nmol/l increased mRNA and protein expression of E-cadherin without cytotoxicity. OXT upregulated mRNA and protein expression of EGR1 in 6 h. p53, phosphatase and tensin, and p21 expression was increased in an EGR1-dependent manner with OXT treatment. In addition, OXT significantly downregulated 3-D spheroids' formation according to spheroids' number and size. Our data showed that OXT downregulated HNSCC cell migration by EGR1 upregulation. OXT inhibited spheroids' formation of HNSCC cells under 3-D culture conditions.

摘要

催产素(OXT)对癌症侵袭的影响存在争议。很少有研究探讨早期生长反应因子-1(EGR1)对头颈部鳞状细胞癌(HNSCC)侵袭的影响。在此,我们评估了EGR1如何通过OXT发挥抗侵袭活性的分子机制来影响HNSCC细胞迁移。采用基质胶侵袭实验和伤口愈合实验来测量体外细胞迁移。通过在HNSCC细胞中敲低或过表达EGR1来评估OXT的分子机制。进行三维(3-D)球体形成,随后进行图像分析以进行定量。500 nmol/l的OXT可增加E-钙黏蛋白的mRNA和蛋白表达,且无细胞毒性。OXT在6小时内上调EGR1的mRNA和蛋白表达。OXT处理后,p53、磷酸酶和张力蛋白以及p21的表达以EGR1依赖的方式增加。此外,根据球体数量和大小,OXT显著下调3-D球体的形成。我们的数据表明,OXT通过上调EGR1来下调HNSCC细胞迁移。在三维培养条件下,OXT抑制HNSCC细胞球体的形成。

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