ATRA increases iodine uptake and inhibits the proliferation and invasiveness of human anaplastic thyroid carcinoma SW1736 cells: Involvement of β-catenin phosphorylation inhibition.
ATRA increases iodine uptake and inhibits the proliferation and invasiveness of human anaplastic thyroid carcinoma SW1736 cells: Involvement of β-catenin phosphorylation inhibition.
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DOI：
10.3892/ol.2017.7225
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发表时间：
2017-12
期刊：
影响因子：
2.9
通讯作者：
Luo Y
中科院分区：
文献类型：
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作者：
Lan L;Basourakos S;Cui D;Zuo X;Deng W;Huo L;Chen H;Zhang G;Deng L;Shi B;Luo Y
全反式维甲酸（ATRA）可以增强甲状腺肿瘤的碘摄取能力，但其机制仍知之甚少。本研究的目的是探讨ATRA对甲状腺未分化癌（ATC）同位素敏感性、增殖和侵袭的影响及其潜在机制。 SW1736细胞用1 µmol/l ATRA或1%乙醇处理5天。建立了稳定表达β-catenin-shRNA的细胞系。使用 125I 进行碘摄取测定。分别使用 MTT 和 Transwell 测定法测试增殖和侵袭性。使用蛋白质印迹法评估 β-连环蛋白、糖原合酶激酶-3β (GSK-3β)、钠/碘同向转运体 (NIS) 和参与上皮间质转化的蛋白质的表达。将用 ATRA 预处理的细胞皮下注射到 SCID 小鼠中。治疗第一天给小鼠腹腔注射131I一次，然后评估肿瘤生长。 131I治疗35天后，与单独131I组相比，ATRA预处理的肿瘤体积和重量均减少（163.32±19.57 vs. 332.06±21.37 mm3；0.35±0.14 vs. 0.67±0.23 g，均P<0.05）。在 β-连环蛋白 shRNA 预处理的肿瘤中观察到类似的结果。 ATRA 还增加了 SW1736 细胞对碘的摄取（P<0.01），并且在 β-catenin shRNA 细胞中也观察到了类似的结果。与对照细胞相比，ATRA处理降低了细胞增殖和侵袭（均P<0.05），与β-catenin shRNA相似。与对照组相比，ATRA 处理降低了磷酸化 (p-)β-连环蛋白、p-GSK-3β、波形蛋白和纤连蛋白的表达，并增加了 NIS 和 E-钙粘蛋白的表达。 ATRA 增加碘摄取并抑制 SW1736 细胞的增殖和侵袭，涉及 β-catenin 磷酸化。总之，ATRA可用于提高ATC的同位素敏感性。
All-trans-retinoic acid (ATRA) can enhance iodine uptake capability of thyroid tumors, but the mechanisms remain poorly understood. The aim of the present study was to investigate the effects of ATRA on isotope susceptibility, proliferation and invasion of anaplastic thyroid carcinoma (ATC) and potential mechanisms. SW1736 cells were treated with 1 µmol/l ATRA or 1% ethanol for 5 days. A cell line stably expressing β-catenin-shRNA was established. An iodine uptake assay was performed using 125I. Proliferation and invasiveness were tested using MTT and Transwell assays, respectively. Western blotting was used to assess the expression of β-catenin, glycogen synthase kinase-3β (GSK-3β), sodium/iodine symporter (NIS) and proteins involved in epithelial-mesenchymal transition. Cells pretreated with ATRA were injected subcutaneously into SCID mice. Mice were intraperitoneally injected with 131I once on the first day of treatment, and tumor growth was then assessed. After 35 days of 131I treatment, ATRA-pretreated tumor volume and weight were decreased compared with the 131I alone group (163.32±19.57 vs. 332.06±21.37 mm3; 0.35±0.14 vs. 0.67±0.23 g, both P<0.05). Similar results were observed in the β-catenin shRNA-pretreated tumors. ATRA also increased the uptake of iodine by SW1736 cells (P<0.01), and similar results were observed in β-catenin shRNA cells. ATRA treatment decreased the cell proliferation and invasion compared with control cells (all P<0.05), similar to β-catenin shRNA. ATRA treatment decreased the expression of phosphorylated (p-)β-catenin, p-GSK-3β, vimentin, and fibronectin, and increased the expression of NIS and E-cadherin, compared with the control. ATRA increased the iodine uptake and inhibited the proliferation and invasion of SW1736 cells, involving β-catenin phosphorylation. In conclusion, ATRA could be used to improve the isotope sensitivity of ATC.
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影响因子：
3.1
作者：
Cheong, Su-Jin;Jang, DooRye;Kim, Dong Wook
通讯作者：
Kim, Dong Wook
影响因子：
4.8
作者：
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影响因子：
3.7
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Ryan J;Curran CE;Hennessy E;Newell J;Morris JC;Kerin MJ;Dwyer RM
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Dwyer RM
影响因子：
4.8
作者：
Furuya, F;Shimura, H;Kobayashi, T
通讯作者：
Kobayashi, T
影响因子：
9
作者：
通讯作者：
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