Sulfasalazine suppresses thyroid cancer cell proliferation and metastasis through T-cell originated protein kinase

柳氮磺吡啶通过 T 细胞来源的蛋白激酶抑制甲状腺癌细胞增殖和转移

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作者:Ling Zou, Zhi Gao, Fanfan Zeng, Juanjuan Xiao, Junmei Chen, Xiaohong Feng, Di Chen, Ying Fang, Jing Cui, Yang Liu, Zhi Li, Feng Zhu, Qiuhong Duan, Xuan Lin

Abstract

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.

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