Department of Nuclear Medicine, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Nucl Med Biol. 2011 Oct;38(7):1053-8. doi: 10.1016/j.nucmedbio.2011.03.001. Epub 2011 Apr 21.
Differentiated thyroid carcinoma (DTC) usually has a high iodine uptake. However, dedifferentiation of DTC with decreased or no radioiodine ((131)I) uptake is observed in clinical practice, with poor prognosis. The aim of this study was to investigate the effects of (131)I radiation on radioiodine uptake (RAIU) and the expression of thyroid-specific molecules.
FTC-133 cells were treated with (131)I, the dosage dictated by methylthiazol tetrazolium test results and preliminary experiments. The experimental cell group was incubated with (131)I for 48 h and then cultured for 3 months in (131)I-free medium. The control group was set without (131)I. Primary cells were defined as the blank group. Following treatment, RAIU was measured with a gamma counter as the counts/cell number. Na(+)/I(-) symporter (NIS), thyroid-stimulating hormone receptor (TSHR), thyroid peroxidase (TPO) and thyroglobulin (Tg) levels were detected by Western blotting and radioimmunoassay, and their mRNAs were detected by real-time polymerase chain reaction.
RAIU of FTC-133 cells decreased gradually after coincubation with (131)I and did not recover even if (131)I was removed. The relative RAIU of the control and experimental groups was 0.567 and 0.182, respectively, a statistically significant difference (P<.01). Expression of NIS, TSHR, TPO and Tg decreased in the experimental group to a statistically significant degree compared to that of controls (P<.05).
Changes in the mRNA levels were in accordance with the expression of thyroid-specific proteins. Thus, FTC-133 cells undergo dedifferentiation during long-term culture in vitro, and (131)I may promote this progress.
分化型甲状腺癌(DTC)通常具有较高的碘摄取率。然而,在临床实践中观察到 DTC 的去分化,其放射性碘摄取(RAIU)减少或无摄取,预后较差。本研究旨在探讨放射性碘(131I)辐射对RAIU 和甲状腺特异性分子表达的影响。
FTC-133 细胞用 131I 处理,剂量根据甲基噻唑四唑试验结果和初步实验确定。实验组孵育 131I 48 小时,然后在无 131I 的培养基中培养 3 个月。对照组未进行 131I 处理。原代细胞作为空白组。处理后,用γ计数器测量 RAIU,以计数/细胞数表示。通过 Western blot 和放射免疫测定法检测钠/碘同向转运体(NIS)、促甲状腺激素受体(TSHR)、甲状腺过氧化物酶(TPO)和甲状腺球蛋白(Tg)的水平,并通过实时聚合酶链反应检测其 mRNAs。
FTC-133 细胞与 131I 共孵育后,RAIU 逐渐下降,即使去除 131I 也未恢复。对照组和实验组的相对 RAIU 分别为 0.567 和 0.182,差异有统计学意义(P<.01)。实验组 NIS、TSHR、TPO 和 Tg 的表达与对照组相比显著下降(P<.05)。
mRNA 水平的变化与甲状腺特异性蛋白的表达一致。因此,FTC-133 细胞在体外长期培养过程中发生去分化,131I 可能促进这一进程。