In Vitro Approaches to Evaluate Placental Drug Transport by Using Differentiating JEG-3 Human Choriocarcinoma Cells
In Vitro Approaches to Evaluate Placental Drug Transport by Using Differentiating JEG-3 Human Choriocarcinoma Cells
复制标题
DOI：
10.1111/j.1742-7843.2010.00634.x
复制
发表时间：
2011-02-01
影响因子：
3.1
通讯作者：
Hirotani, Yoshihiko
中科院分区：
文献类型：
--
作者：
Ikeda, Kenji;Utoguchi, Naoki;Hirotani, Yoshihiko
人绒毛膜癌细胞已被用作研究药物通过胎盘滋养层细胞转运的模型。然而，这些模型允许低分子量药物通过细胞间间隙连接转运。本研究旨在探讨JEG-3绒毛膜癌细胞在不同培养条件下的分化模式，建立合适的体外合体滋养层药物转运模型。通过测量跨JEG-3细胞层的跨上皮电阻（TEER）来估计细胞旁渗透性。绒毛膜癌非表达克隆1（NECC 1）和乳腺癌耐药蛋白（BCRP）的mRNA表达水平以及与从细胞滋养层分化的合体滋养层细胞融合能力相关的粘附连接相关蛋白E-钙粘蛋白（ECAD）和钙粘蛋白-11（CDH 11）的mRNA表达水平被认为是分化信号。在Dulbecco改良Eagle培养基（DMEM）/Ham F-12（1：1）混合培养基（CS-C（R）; Dainippon Sumitomo Pharma Co. Ltd.，日本大坂）。通过比较TEER值和分化信号，作者确定了至少五种JEG-3细胞分化模式。在CS-C中培养的JEG-3的分化模式类似于体内合胞体滋养细胞样分化信号特征。总之，在CS-C中培养的分化JEG-3细胞的合胞体滋养层样模型可能适合于评估药物通过胎盘滋养层的转运。
Human choriocarcinoma cells have been used as models for studying transcellular drug transport through placental trophoblasts. However, these models allow the transport of low-molecular-weight drugs through intercellular gap junctions. This study aimed at investigating the differentiation patterns of JEG-3 choriocarcinoma cells under different culture conditions and establishing the appropriate model of in vitro syncytiotrophoblast drug transport. Paracellular permeability was estimated by measuring the transepithelial electrical resistance (TEER) across JEG-3 cell layers. The mRNA expression levels of non-expressed in choriocarcinoma clone 1 (NECC1) and breast cancer resistance protein (BCRP), and those of E-cadherin (ECAD) and cadherin-11 (CDH11), which are adherens junction-associated proteins related to fusogenic ability of syncytiotrophoblasts differentiated from cytotrophoblasts, protein expression levels were considered as the differentiation signals. The highest TEER values were obtained in the JEG-3 cells cultured in the Dulbecco's modified Eagle's medium (DMEM)/Ham's F-12 (1:1) mixed medium (CS-C (R); Dainippon Sumitomo Pharma Co. Ltd., Osaka, Japan). By comparing the TEER values and the differentiation signals, the authors identified at least five JEG-3 cell-differentiation patterns. The differentiation pattern of JEG-3 cultured in CS-C resembled the syncytiotrophoblast-like differentiation signal characterizations in vivo. In conclusion, the syncytiotrophoblast-like models of differentiating JEG-3 cells cultured in CS-C might be appropriate for evaluating drug transport across the placental trophoblast.