Anti-fungal drug itraconazole exerts anti-cancer effects in oral squamous cell carcinoma via suppressing Hedgehog pathway

Abstract

Aims: To investigate the therapeutic potential of itraconazole in oral squamous cell carcinoma (OSCC) and its molecular mechanism.

Materials and methods: The in vitro anti-cancer effects of itraconazole was determined by CCK-8 assay and colony formation assay. Transwell and wound healing assays were used to examine cell invasion and migration. The in vivo therapeutic efficacy of itraconazole was assessed by OSCC patient-derived xenograft (PDX) model. Western blot was performed to explore the anti-cancer mechanism.

Key findings: Itraconazole inhibited cell proliferation and colony formation of OSCC cells in a time and concentration dependent manner; induced cell cycle arrest and apoptosis, as well as inhibited cell invasion and migration. In the OSCC PDX model, itraconazole impeded tumor growth, reduced Ki-67 expression and induced apoptosis. Itraconazole downregulated the protein expression of Hedgehog pathway to inhibit proliferation and migration of oral squamous cell carcinoma cells, which can be revised by recombinant human sonic hedgehog protein (rSHH).

Significance: Itraconazole showed anti-cancer effects on OSCC via inhibiting the Hedgehog pathway.

Keywords: Hedgehog pathway; Itraconazole; Oral squamous cell carcinoma; Patient-Derived Xenograft.