Shin Sam, Go Ryeo-Eun, Kim Cho-Won, Hwang Kyung-A, Nam Ki-Hoan, Choi Kyung-Chul
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.
Food Chem Toxicol. 2016 Jul;93:58-65. doi: 10.1016/j.fct.2016.04.026. Epub 2016 May 1.
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.
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。