ET-69 * SPECIFIC Wip1 INHIBITOR, CCT007093 ABROGATE CELL PROLIFERATION, MIGRATION AND INVASION INDUCED BY THE UVC RADIATION IN HUMAN GLIOBLASTOMA CELLS

Abstract

BACKGROUND: Wild-type p53-induced phosphatase (Wip1) is induced in response to stress, DNA damage. Wip1 was frequently overexpressed or amplified in breast cancer, ovarian cancer, neuroblastomas, and was accounted for poor prognosis in glioma patients. Little was known how Wip1 performed when exposed to UVC radiation in human glioblastoma cells. METHODS: Human glioblastoma Cells (U87, U251) were exposed to UVC irradiation with doses of UVC as 0,1,5,25,50 and 100 J J/m2 (J) at 254 nm. Cell proliferation of U87, U251 cells exposed to UVC radiation was investigated. And Cell viability of the U87, U251 cells subjected with CCT007093, specific Wip1 inhibitor, in doses of 0, 5, 25, 50, 100, 200 µM was modulated by CCK-8 assay. Then U87, U251 cells were subjected with 50 J per m2 of UVC irradiation combined with CCT007093, and the expression of p53, Wip1 and p38 was checked. Also the cell invasion and migration exposed to UVC combined with CCT007093 were investigated by transwell and scracth assay. RESULTS: When exposed with doses above 25, the proliferation of U87, U251 cell were inhibited obviously. The exposure to UVC radiation significantly upregulated Wip1 protein level in U87, U251 cells within 24 hours. When subjected to dose of 50 J/m2 UVC combined with 50 µM CCT007093, the protein expression of Wip1, p53 were up-regulated accompany with the downregulation of p38 protein, CCT007093 could block the expression of Wip1 induced by UVC especially in U87 cell. Meanwhile CCT007093 contributed to the inhibition of glioma cell migration and invasion induced by UVC in vitro. CONCLUSIONS: The up-regulation of Wip1 in glioblastoma cells due to UVC damage could be partly attributed to the function of p53. CCT007093, specific Wip1 inhibitor, could synergy UVC irradiation to inhibit cell proliferation, migration and invasion in human glioblastoma cells.