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二苯甲酮-1和辛基酚对雌激素受体表达的卵巢癌细胞中通过雌激素受体依赖性途径调节上皮-间质转化的影响。

Effect of benzophenone-1 and octylphenol on the regulation of epithelial-mesenchymal transition via an estrogen receptor-dependent pathway in estrogen receptor expressing ovarian cancer cells.

作者信息

Shin Sam, Go Ryeo-Eun, Kim Cho-Won, Hwang Kyung-A, Nam Ki-Hoan, Choi Kyung-Chul

机构信息

Laboratory of Biochemistry and Immunology, College of Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.

Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk, Republic of Korea.

出版信息

Food Chem Toxicol. 2016 Jul;93:58-65. doi: 10.1016/j.fct.2016.04.026. Epub 2016 May 1.

Abstract

Epithelial-mesenchymal transition (EMT) is an important process in embryonic development and cancer progression and metastasis. EMT is influenced by 17β-estradiol (E2), an endogenous estrogen. Benzophenone-1 (2,4-dihydroxybenzophenone, BP-1) and 4-tert-octylphenol (OP) are suspected endocrine disrupting chemicals (EDCs) because they can exhibit estrogenic properties. In this study, we examined whether BP-1 and OP can lead to EMT of BG-1 ovarian cancer cells expressing estrogen receptors (ERs). A wound healing assay and western blot assay were conducted to show the effect of BP-1 and OP on the migration of BG-1 cells and protein expression of EMT-related genes. BP-1 (10(-6) M) and OP (10(-6) M) significantly enhanced the migration capability of BG-1 cells by reducing the wounded area in the cell monolayer relative to the control, similar to E2 (10(-9) M). However, when BG-1 cells were co-treated with ICI 182,780, an ER antagonist, the uncovered area was maintained at the level of the control. N-cadherin, snail, and slug were increased by BP-1 and OP while E-cadherin was reduced compared to the control. However, this effect was also restored by co-treatment with ICI 182,780. Taken together, these results indicate that BP-1 and OP, the potential EDCs, may have the ability to induce ovarian cancer metastasis via regulation of the expression of EMT markers and migration of ER-expressing BG-1 ovarian cancer cells.

摘要

上皮-间质转化(EMT)是胚胎发育以及癌症进展和转移过程中的一个重要过程。EMT受内源性雌激素17β-雌二醇(E2)影响。二苯甲酮-1(2,4-二羟基二苯甲酮,BP-1)和4-叔辛基苯酚(OP)被怀疑是内分泌干扰化学物质(EDCs),因为它们可表现出雌激素特性。在本研究中,我们检测了BP-1和OP是否能导致表达雌激素受体(ERs)的BG-1卵巢癌细胞发生EMT。进行了伤口愈合试验和蛋白质印迹试验,以显示BP-1和OP对BG-1细胞迁移以及EMT相关基因蛋白质表达的影响。与对照相比,BP-1(10⁻⁶ M)和OP(10⁻⁶ M)通过减少细胞单层中的伤口面积,显著增强了BG-1细胞的迁移能力,类似于E2(10⁻⁹ M)。然而,当BG-1细胞与ER拮抗剂ICI 182,780共同处理时,未覆盖面积维持在对照水平。与对照相比,BP-1和OP使N-钙黏蛋白、蜗牛蛋白和蛞蝓蛋白增加,而E-钙黏蛋白减少。然而,与ICI 182,780共同处理也恢复了这种效应。综上所述,这些结果表明,潜在的内分泌干扰化学物质BP-1和OP可能具有通过调节EMT标志物的表达以及ER表达的BG-1卵巢癌细胞的迁移来诱导卵巢癌转移的能力。

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