pai-039 and Head-and-Neck-Neoplasms

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.. 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.. 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.. 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. © 2015 Wiley Periodicals, Inc. Head Neck 38: E895-E904, 2016.

Topics: Cell Line, Tumor; Enhancer Elements, Genetic; Gene Knockdown Techniques; Head and Neck Neoplasms; Humans; Indoleacetic Acids; Neoplastic Stem Cells; Plasminogen Activator Inhibitor 1; Promoter Regions, Genetic; Real-Time Polymerase Chain Reaction; RNA, Small Interfering; SOXB1 Transcription Factors