Yueh-Chun Lee1,2, Cheng-Chia Yu3,4,5, Chih Lan6, Che-Hsin Lee7,8, Hsueh-Te Lee9, Yu-Liang Kuo10,11, Po-Hui Wang2,12,13, Wen-Wei Chang6,14. 1. Radiation Oncology Department, Chung Shan Medical University Hospital, Taichung City, Taiwan. 2. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. 3. School of Dentistry, Chung Shan Medical University, Taichung, Taiwan. 4. Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan. 5. Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan. 6. School of Biomedical Sciences, Chung Shan Medical University, Taichung City, Taiwan. 7. Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung, Taiwan. 8. Department of Microbiology, School of Medicine, China Medical University, Taichung, Taiwan. 9. Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming University, Taipei, Taiwan. 10. Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan. 11. School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan. 12. Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan. 13. School of Medicine, Chung Shan Medical University, Taichung, Taiwan. 14. Department of Medical Research, Chung Shan Medical University Hospital, Taichung City, Taiwan.
Abstract
BACKGROUND: The existence of tumor-initiating cells (TICs) has been described in head and neck cancers. Plasminogen activator inhibitor-1 (PAI-1) has been demonstrated to act as a prognostic factor in head and neck cancers. METHODS: Tiplaxtinin (PAI-039), a specific inhibitor of PAI-1, and PAI-1-specific siRNA were used to examine the role of PAI-1 in the self-renewal property of head and neck cancer-TICs by tumorsphere formation. Western blot, real-time polymerase chain reaction, and luciferase-based reporter assay were used to study the effect of PAI-039 in the sex-determining region Y-box 2 (Sox2) expression. RESULTS: PAI-039 suppressed the self-renewal capability of head and neck cancer-TICs derived from head and neck cancer cell lines through the inhibition of Sox2 expression. PAI-039 decreased the activity of the core promoter and the enhancer of the Sox2 gene in head and neck cancer-TICs. Knockdown of PAI-1 expression also inhibited self-renewal and radioresistance properties of head and neck cancer-TICs. CONCLUSION: The inhibition of PAI-1 by PAI-039 or siRNA could suppress head and neck cancer-TICs within head and neck cancer cell lines through the downregulation of Sox2.
BACKGROUND: The existence of tumor-initiating cells (TICs) has been described in head and neck cancers. Plasminogen activator inhibitor-1 (PAI-1) has been demonstrated to act as a prognostic factor in head and neck cancers. METHODS:Tiplaxtinin (PAI-039), a specific inhibitor of PAI-1, and PAI-1-specific siRNA were used to examine the role of PAI-1 in the self-renewal property of head and neck cancer-TICs by tumorsphere formation. Western blot, real-time polymerase chain reaction, and luciferase-based reporter assay were used to study the effect of PAI-039 in the sex-determining region Y-box 2 (Sox2) expression. RESULTS:PAI-039 suppressed the self-renewal capability of head and neck cancer-TICs derived from head and neck cancer cell lines through the inhibition of Sox2 expression. PAI-039 decreased the activity of the core promoter and the enhancer of the Sox2 gene in head and neck cancer-TICs. Knockdown of PAI-1 expression also inhibited self-renewal and radioresistance properties of head and neck cancer-TICs. CONCLUSION: The inhibition of PAI-1 by PAI-039 or siRNA could suppress head and neck cancer-TICs within head and neck cancer cell lines through the downregulation of Sox2.
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