Dexmedetomidine Regulates Proliferation, Apoptosis, Migration, and Invasion in Ovarian Cancer Cells via MiR-155-HIF-1α Axis
Lihong Zheng, Ruimei Jia, Juan Zhao
Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China (mainland)
Med Sci Monit 2019; 25:10164-10172
Dexmedetomidine (DMED) is widely used as an adjuvant anesthetic, but how DMED regulates biological behavior of OC cells remains an area of active research. This study investigated the mechanism by which DMED regulates the proliferation, apoptosis, migration, and invasion abilities of OC cells.
MATERIAL AND METHODS: We determined the optimal concentration of DMED for use in treating SKOV3 cells. The biological activities of DMED-treated SKOV3 cells following transfection with miR-155 inhibitor or si-HIF-1alpha were measured by CCK-8 assay, flow cytometry, wound healing assay, and Transwell assay. qRT-PCR and Western blot analysis were performed to assess the expression levels of apoptotic-related caspase-3 and Mcl-1. Luciferase reporter assay verified the targeting relationship of miR-155 and HIF-1alpha.
RESULTS: miR-155 was downregulated while HIF-1alpha was upregulated in SKOV3 cells. DMED dose-dependently reduced HIF-1alpha expression in SKOV3 cells, and upregulated the expression of miR-155. DMED inhibited the proliferation, migration and invasion abilities of OC cells, but also contributed to apoptosis of SKOV3 cells, while transfection of miR-155 inhibitor inhibited the effect of DMED on SKOV3 cells. In contrast, transfection with si-HIF-1alpha enhanced the effects of DMED on SKOV3 cells. HIF-1alpha was found to be a target gene of miR-155.
CONCLUSIONS: Our results suggest that DMED blocks cell proliferation, migration, and invasion and accelerates cell apoptosis in OC.
Keywords: Apoptosis, Cell Migration Assays, Cell Proliferation, dexmedetomidine, Ovarian Neoplasms