Zhang Min, Guo Rui, Xu Haoping, Zhang Miao, Li Biao
Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Nucl Med Commun. 2011 Jul;32(7):605-10. doi: 10.1097/MNM.0b013e3283463027.
Radioiodine ablation is ineffective in patients with radioiodine nonresponsive thyroid carcinoma. We investigated the effects of all-trans retinoic acid (ATRA) combined with histone deacetylase inhibitor, tributyrin on sodium-iodide symporter (NIS) expression, radioiodine uptake, and inhibition of cell proliferation in a poorly differentiated follicular thyroid carcinoma (FTC-133) in vitro.
FTC-133 cells were cultured in the presence of ATRA and tributyrin either as a single agent or in combinations for 48 h. The expression of NIS mRNA and protein was, respectively, detected by quantitative real-time polymerase chain reaction and western blot. The radioiodine uptake was determined after incubation of FTC-133 cells with 125I-iodide. Finally, the cell proliferation test of FTC-133 was performed after treatment.
Enhanced expression of NIS mRNA and protein was observed in FTC-133 cells treated with ATRA and tributyrin, which further resulted in significant higher levels of radioiodine uptake than that of untreated control cells and cells treated with ATRA alone. Additive inhibition of the proliferation of FTC-133 cells was also observed with the combination of ATRA and tributyrin.
The combination of ATRA and tributyrin induced a synergistic effect on radioiodine uptake and inhibition of FTC-133 cells proliferation in vitro. However, further in-vivo studies and additional molecular research will be needed to determine the absolute efficiency of radioiodine therapy.
放射性碘消融对放射性碘无反应的甲状腺癌患者无效。我们在体外研究了全反式维甲酸（ATRA）联合组蛋白去乙酰化酶抑制剂三丁酸甘油酯对低分化滤泡状甲状腺癌（FTC-133）钠-碘同向转运体（NIS）表达、放射性碘摄取及细胞增殖抑制的影响。
将FTC-133细胞在ATRA和三丁酸甘油酯单独或联合存在的情况下培养48小时。分别通过定量实时聚合酶链反应和蛋白质印迹法检测NIS mRNA和蛋白质的表达。在用125I-碘化物孵育FTC-133细胞后测定放射性碘摄取。最后，在处理后进行FTC-133的细胞增殖试验。
在用ATRA和三丁酸甘油酯处理的FTC-133细胞中观察到NIS mRNA和蛋白质表达增强，这进一步导致放射性碘摄取水平显著高于未处理的对照细胞和单独用ATRA处理的细胞。ATRA和三丁酸甘油酯联合使用还观察到对FTC-133细胞增殖的相加抑制作用。
ATRA和三丁酸甘油酯联合使用在体外对放射性碘摄取和FTC-133细胞增殖抑制具有协同作用。然而，需要进一步的体内研究和更多的分子研究来确定放射性碘治疗的绝对疗效。
