Albany College of Pharmacy and Health Sciences, Pharmaceutical Research Institute, Rensselaer, New York 12144, USA.
Thyroid. 2010 Mar;20(3):281-6. doi: 10.1089/thy.2009.0249.
Tetraiodothyroacetic acid (tetrac) is a deaminated analogue of L-thyroxine that blocks the actions of L-thyroxine and 3,5,3'-triiodo-L-thyronine at the cell surface receptor for thyroid hormone on integrin alpha v beta 3. Tetrac blocks the proliferative effects of thyroid hormone on tumor cells and the proangiogenesis actions of the hormone. In the absence of thyroid hormone, tetrac also blocks angiogenesis induced by various growth factors. Covalently linked to poly(lactide-co-glycolide), tetrac nanoparticles (tetrac NP) do not gain access to the cell interior and act exclusively at the integrin receptor. Here, the activity of tetrac and tetrac NP against follicular thyroid carcinoma (FTC)-236 cells was studied in two models: (1) tumor cell implants in the chick chorioallantoic membrane (CAM) system and (2) xenografts in the nude mouse.
FTC-236 cells (10(6)) were implanted in the CAM (n = 8 each for control, and for tetrac and tetrac NP, both at 1 microg/CAM) and the actions of tetrac and tetrac NP were determined after 8 days on tumor-related angiogenesis and tumor growth. Xenografts of 10(7) FTC-236 cells were implanted in nude mice (n = 8 per group). Tetrac or tetrac NP was administered intraperitoneal (1 mg/kg and 1 mg tetrac equivalent/kg, respectively) every other day for 32 days beginning on day 10, when tumor volume was 200-250 mm(3). Animals were monitored after discontinuation of treatment up to day 40.
In the CAM paradigm, tetrac and tetrac NP arrested tumor-related angiogenesis and tumor growth. In the xenograft model, tetrac and tetrac NP promptly and progressively reduced tumor volume (p < 0.01) over 32 days. There was some regrowth of tumor after interruption of tetrac treatment, but at day 40, tumor volume and tumor weight at sacrifice were 45-55% below those of controls (p < 0.01). Animal weight gain was comparable in the control and treatment groups of animals.
Tetrac and tetrac NP effectively arrest FTC-236 cell tumor growth in the CAM and xenograft models, suggesting its potential utility against FTC.
四碘甲状腺原氨酸乙酸盐（tetrac）是 L-甲状腺素的脱氨类似物，可阻断 L-甲状腺素和 3,5,3'-三碘-L-甲状腺素在甲状腺激素细胞表面受体上对整合素 α v β 3 的作用。tetrac 阻断甲状腺激素对肿瘤细胞的增殖作用和激素的促血管生成作用。在没有甲状腺激素的情况下，tetrac 还阻断各种生长因子诱导的血管生成。与聚（乳酸-共-乙醇酸）共价连接的 tetrac 纳米颗粒（tetrac NP）无法进入细胞内部，仅在整合素受体上发挥作用。在这里，研究了 tetrac 和 tetrac NP 在两种模型中对滤泡性甲状腺癌（FTC）-236 细胞的活性：（1）鸡胚绒毛尿囊膜（CAM）系统中的肿瘤细胞植入物和（2）裸鼠中的异种移植物。
将 10^6 FTC-236 细胞植入 CAM（每组各 8 只用于对照，以及 1 μg/CAM 的 tetrac 和 tetrac NP），并在第 8 天测定 tetrac 和 tetrac NP 对肿瘤相关血管生成和肿瘤生长的作用。将 10^7 FTC-236 细胞的异种移植物植入裸鼠（每组 8 只）。从第 10 天开始，当肿瘤体积为 200-250mm^3 时，每隔一天腹膜内注射 1mg/kg 和 1mg 等效 tetrac/kg 的 tetrac 或 tetrac NP，共 32 天。在停止治疗后直至第 40 天监测动物。
在 CAM 范式中，tetrac 和 tetrac NP 阻止了肿瘤相关的血管生成和肿瘤生长。在异种移植模型中，tetrac 和 tetrac NP 迅速且逐渐减少肿瘤体积（p <0.01），持续 32 天。在 tetrac 治疗中断后，肿瘤有一些再生，但在第 40 天，处死时的肿瘤体积和肿瘤重量比对照组低 45-55%（p <0.01）。动物体重增加在对照组和治疗组动物中是相当的。
tetrac 和 tetrac NP 有效地阻止了 FTC-236 细胞在 CAM 和异种移植模型中的肿瘤生长，这表明其在治疗 FTC 方面具有潜在的应用价值。
Zotero 插件