Sulfasalazine suppresses thyroid cancer cell proliferation and metastasis through T-cell originated protein kinase
Sulfasalazine suppresses thyroid cancer cell proliferation and metastasis through T-cell originated protein kinase
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柳氮磺吡啶通过 T 细胞源性蛋白激酶抑制甲状腺癌细胞增殖和转移
DOI：
10.3892/ol.2019.10721
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发表时间：
2019-10-01
期刊：
影响因子：
2.9
通讯作者：
Lin, Xuan
中科院分区：
文献类型：
--
作者：
Zou, Ling;Gao, Zhi;Lin, Xuan
放射性碘难治性或快速进展的甲状腺癌患者需要有效的治疗。T细胞来源的蛋白激酶（TOPK）在许多不同的肿瘤类型中高度表达，其中它促进增殖和转移。然而，TOPK在甲状腺癌中的表达很少被记录。因此，我们采用免疫组化方法检测甲状腺癌组织中TOPK的表达，并探讨其在甲状腺癌中的临床意义。柳氮磺胺吡啶是一种TOPK的靶向抑制剂，直接与蛋白质结合，解离常数（Kd）为228 µ M，也使用微型热泳进行了研究。柳氮磺胺吡啶抑制TOPK活性，如通过体外下拉测定所确定的。柳氮磺胺吡啶还能抑制甲状腺癌细胞的增殖和转移。提示TOPK可能是甲状腺癌潜在的治疗靶点和诊断生物标志物，并可作为评价甲状腺结节恶性程度的指标。因此，柳氮磺胺吡啶是一种潜在的甲状腺癌靶向治疗的新化合物。
Thyroid cancer patients with radioactive iodine-refractory or rapidly progressing presentation require effective treatment. T-cell originated protein kinase (TOPK) is highly expressed in a number of different tumor types, where it promotes proliferation and metastasis. However, the expression of TOPK in thyroid cancer is poorly documented. Therefore, immunohistochemistry was used to detect the expression of TOPK in thyroid cancer tissues, and its clinical significance in this disease was investigated. Sulfasalazine, a targeted inhibitor of TOPK that directly binds the protein with a dissociation constant (Kd) of 228 µM, was also investigated using microscale thermophoresis. Sulfasalazine inhibited TOPK activity, as determined by an in vitro pull-down assay. Furthermore, sulfasalazine inhibited the proliferation and metastasis of thyroid cancer cells. The results indicated that TOPK may be a potential therapeutic target and diagnostic biomarker for thyroid cancer and may be used as an index to evaluate malignant thyroid nodules. Therefore, sulfasalazine is a potential novel compound for the targeted treatment of thyroid cancer.