Resumen
The efficiency of cisplatin is limited by drug resistance in head?neck cancer (HNC) patients. In this study, we established a cisplatin resistance (CR) cell model, generated CR related transcriptome profiling, and combined application of bioinformatics methodology to discover a possible way to overcome CR. Analysis of the functional pathway revealed that mitotic division is a novel mechanism significantly contributing to CR. Spindle pole body component 25 (SPC25), a kinetochore protein, was overexpressed in CR cells and significantly correlated with worse HNC patient survival. The silencing of SPC25 increased cisplatin sensitivity and reduced cancer stemness property. Integration of CR transcriptome profiling and drug database discovered a natural extract compound, celastrol, possessing a potent cytotoxic effect in CR cells to reverse CR. Thus, we combined systemic strategies to demonstrated that a novel biological process (mitotic cell division), a hub gene (SPC25), and a natural compound (celastrol) as novel strategies for the treatment of refractory HNC.