Anti-cancer effect of midazolam via downregulating YWHAH in papillary thyroid cancer cells

Abstract

Abstract The work is aimed to investigate whether midazolam functions in thyroid cancer and reveal the potential mechanism of action. Cell viability was detected by CCK-8 method when treated by varying doses of midazolam to detect the cytotoxicity of midazolam on human thyroid follicular epithelial cell line and thyroid cancer cell lines. In thyroid cancer cells, EDU staining, wound healing and transwell assays were respectively used to detect cell proliferation, migration and invasion. Western blot was used to detect the expressions of matrix metalloproteinases (MMPs). Flow cytometry assay, western blot and immunofluorescence staining were used to detect cell apoptosis. CB-Dock2 server predicted midazolam-tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH) interaction and western blot was also used to detect YWHAH expression. Midazolam dose-dependently decreased the viability of thyroid cancer cells and demonstrated no cytotoxicity on Nthy-ori-3-1 cells. In addition, increasing concentrations of midazolam or silencing of YWHAH significantly inhibited thyroid cancer cell proliferation, migration and invasion and induced cell apoptosis. Midazolam had a molecular binding with YWHAH and midazolam downregulated YWHAH expression. YWHAH partially reversed the impacts of midazolam on the cellular events in thyroid cancer. Collectively, midazolam may act as an anti-thyroid cancer agent via its interrelation with YWHAH.

Keywords

• Invasion
• Midazolam
• Migration
• Thyroid cancer
• YWHAH