Lan Ling, Basourakos Spyros, Cui Dai, Zuo Xuemei, Deng Wei, Huo Lili, Chen Hailing, Zhang Guoying, Deng Lili, Shi Bingyin, Luo Yong
Department of Endocrinology, Beijing Jishuitan Hospital, Beijing 100035, P.R. China.
Department of Genitourinary, Cancer Medicine, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA.
Oncol Lett. 2017 Dec;14(6):7733-7738. doi: 10.3892/ol.2017.7225. Epub 2017 Oct 19.
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 I. 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 I once on the first day of treatment, and tumor growth was then assessed. After 35 days of I treatment, ATRA-pretreated tumor volume and weight were decreased compared with the I alone group (163.32±19.57 vs. 332.06±21.37 mm; 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.
全反式维甲酸（ATRA）可增强甲状腺肿瘤的碘摄取能力，但其机制仍知之甚少。本研究旨在探讨ATRA对间变性甲状腺癌（ATC）同位素敏感性、增殖和侵袭的影响及其潜在机制。将SW1736细胞用1μmol/l ATRA或1%乙醇处理5天。建立稳定表达β-连环蛋白短发夹RNA（shRNA）的细胞系。使用碘进行碘摄取试验。分别使用MTT和Transwell试验检测增殖和侵袭能力。采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）以及参与上皮-间质转化的蛋白质的表达。将经ATRA预处理的细胞皮下注射到严重联合免疫缺陷（SCID）小鼠体内。在治疗的第一天，小鼠腹腔注射一次碘，然后评估肿瘤生长情况。碘治疗35天后，与单纯碘治疗组相比，经ATRA预处理的肿瘤体积和重量均减小（分别为163.32±19.57 vs. 332.06±21.37 mm；0.35±0.14 vs. 0.67±0.23 g，均P<0.05）。在经β-连环蛋白shRNA预处理的肿瘤中也观察到类似结果。ATRA还增加了SW1736细胞对碘的摄取（P<0.01），在β-连环蛋白shRNA细胞中也观察到类似结果。与对照细胞相比，ATRA处理降低了细胞增殖和侵袭能力（均P<0.05），与β-连环蛋白shRNA情况相似。与对照相比，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-钙黏蛋白的表达。ATRA增加碘摄取并抑制SW1736细胞的增殖和侵袭，涉及β-连环蛋白磷酸化。总之，ATRA可用于提高ATC的同位素敏感性。
