Fortunati Nicoletta, Catalano Maria G, Arena Katia, Brignardello Enrico, Piovesan Alessandro, Boccuzzi Giuseppe
Oncological Endocrinology, ASO San Giovani Battista, University of Turin, Italy.
J Clin Endocrinol Metab. 2004 Feb;89(2):1006-9. doi: 10.1210/jc.2003-031407.
In poorly differentiated thyroid cancer, molecular characteristics are reported to be lost such as to cause insensitivity of the tumor to radiometabolic therapy. Considerable work is in progress to identify compounds that redifferentiate thyroid cancer cells. The present study evaluates the action of valproic acid, a potent anticonvulsant recently reported to inhibit histone deaceytlase, on cultured thyroid cancer cells. N-PA (poorly differentiated) and ARO (anaplastic) cells were treated with increasing valproic acid concentrations.; expression of mRNA and cell localization pattern for the Na+/I- symporter (NIS), as well as 125I uptake, were evaluated before and after treatment. Valproic acid induced NIS gene expression, NIS membrane localization and iodide accumulation in N-PA cells; it was effective at clinically-safe doses in the therapeutic range. In ARO cells, only induction of NIS mRNA was observed, and was not followed by any change in iodide uptake. Valproic acid is thus effective at restoring the ability of N-PA cells to accumulate iodide and its use in clinical trials may be recommended.
在低分化甲状腺癌中，据报道分子特征丧失，导致肿瘤对放射性代谢疗法不敏感。目前正在进行大量工作以鉴定能使甲状腺癌细胞重新分化的化合物。本研究评估了丙戊酸（一种最近报道可抑制组蛋白脱乙酰酶的强效抗惊厥药）对培养的甲状腺癌细胞的作用。用递增浓度的丙戊酸处理N-PA（低分化）和ARO（间变性）细胞；在处理前后评估钠/碘同向转运体（NIS）的mRNA表达和细胞定位模式以及125I摄取。丙戊酸诱导N-PA细胞中NIS基因表达、NIS膜定位和碘积累；在治疗范围内的临床安全剂量下有效。在ARO细胞中，仅观察到NIS mRNA的诱导，且碘摄取无任何变化。因此，丙戊酸在恢复N-PA细胞积累碘的能力方面有效，可能推荐其用于临床试验。
