Triptonide inhibits the progression of oral squamous cell carcinoma by suppressing the TRIP13/c-Myc axis.

Abstract

Triptonide, an active ingredient of Tripterygium wilfordii Hook. F., has been found to have anticancer effects on various cancers; however, its effect on oral squamous cell carcinoma (OSCC) has not yet been studied. This study aims to reveal the effect and mechanism of triptonide on OSCC. The inhibitory effect of triptonide on OSCC progression was ascertained by CCK-8 assay, EdU incorporation assay, wound healing assay, Transwell assay, and xenograft tumor model, while western blotting, qRT-PCR, and immunohistochemistry revealed that triptonide could inhibit c-Myc expression in OSCC. RNA-seq was conducted to explore the mechanism by which triptonide inhibited the progression of OSCC, and thyroid hormone receptor interactor 13 (TRIP13) was identified as a key differentially expressed gene. TRIP13-knockdown OSCC cells constructed with siRNA showed weaker progression ability in CCK-8 assay, EdU incorporation assay, wound healing assay, and Transwell assay. Finally, TRIP13-overexpressing OSCC cells constructed through plasmid were used in rescue experiments, which demonstrated that TRIP13 was located upstream of c-Myc and the overexpression of TRIP13 could partially restore the decreased c-Myc expression caused by triptonide treatment. Collectively, this study demonstrated that triptonide might reduce the expression of c-Myc by suppressing TRIP13 expression, thereby inhibiting the progression of OSCC. These findings have revealed a partial mechanism by which triptonide acts on OSCC and suggested its potential application value in OSCC treatment.