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Orthotopic Inoculation of Thyroid Cancer Cells into Murine Thyroid: A Procedure to Establish Orthotopic Thyroid Cancer Mouse Model
Published on: April 30, 2023
Sulfasalazine suppresses thyroid cancer cell proliferation and metastasis through T-cell originated protein kinase
Ling Zou1,2, Zhi Gao1, Fanfan Zeng2
1Department of Internal Medicine, CR and WISCO General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430080, P.R. China.
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.
Insights
T-cell originated protein kinase (TOPK) is highly expressed in thyroid cancer. Targeting TOPK with sulfasalazine may offer a novel therapeutic strategy for treating thyroid cancer, including its proliferation and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Thyroid cancer necessitates effective treatments, especially for radioactive iodine-refractory or rapidly progressing cases.
- T-cell originated protein kinase (TOPK) is implicated in various cancers, promoting proliferation and metastasis.
- TOPK expression and significance in thyroid cancer remain underexplored.
Purpose of the Study:
- To investigate TOPK expression in thyroid cancer tissues.
- To evaluate the clinical significance of TOPK in thyroid cancer.
- To assess sulfasalazine as a potential TOPK inhibitor for thyroid cancer treatment.
Main Methods:
- Immunohistochemistry was employed to detect TOPK expression in thyroid cancer.
- Microscale thermophoresis characterized the binding of sulfasalazine to TOPK.
- In vitro pull-down assays and cell-based assays assessed TOPK activity, proliferation, and metastasis.
Main Results:
- TOPK is expressed in thyroid cancer tissues, suggesting clinical significance.
- Sulfasalazine directly binds and inhibits TOPK activity.
- Sulfasalazine demonstrated inhibitory effects on thyroid cancer cell proliferation and metastasis.
Conclusions:
- TOPK represents a potential therapeutic target and diagnostic biomarker for thyroid cancer.
- TOPK may serve as an index for evaluating malignant thyroid nodules.
- Sulfasalazine shows promise as a novel therapeutic agent for targeted thyroid cancer treatment.
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