Modulation of Sonic hedgehog signaling and WW domain containing oxidoreductase XXXX expression enhances radiosensitivity of @entity1 @entity463 cells.

@entity1 @entity5 @entity8889 @entity876 @entity4851 @entity463 @entity6714 @entity19702
UNASSIGNED: WW domain containing oxidoreductase, designated @entity19702 , FOR or @entity19702 , is a known pro-apoptotic factor when ectopically expressed in various types of @entity5 cells, including @entity463 ( @entity463 ). The activation of sonic hedgehog ( @entity4851 ) signaling, especially paracrine @entity4851 secretion in response to radiation, is associated with impairing the effective irradiation of @entity5 cells. Here, we examined the role of @entity4851 signaling and @entity19702 overexpression in the radiosensitivity of @entity1 @entity463 cells. Our results showed that ionizing irradiation (IR) increased the cytoplasmic @entity4851 and nuclear @entity8889 content in @entity463 U373MG and U87MG cells. @entity463 cells with exogenous @entity4851 treatment exhibited similar results. Pretreatment with @entity4851 peptides protected U373MG and U87MG cells against IR in a dose-dependent manner. Cyclopamine, a Hedgehog/Smoothened (SMO) inhibitor, reversed the protective effect of @entity4851 in U87MG cells. Cyclopamine increased @entity4851 plus IR-induced @entity6714 , a marker of DNA double-strand breaks, in these cells. To verify the role of @entity4851 signaling in the radiosensitivity of @entity463 cells, we tested the effect of the @entity8889 ( @entity8889 ) inhibitor zerumbone and found that it could sensitize @entity463 cells to IR. We next examined the role of @entity19702 in radiosensitivity. Overexpression of @entity19702 enhanced the radiosensitivity of U87MG (possessing wild type @entity876 or WTp53) but not U373MG (harboring mutant @entity876 or MTp53) cells. Pretreatment with @entity4851 peptides protected both @entity19702 -overexpressed U373MG and U87MG cells against IR and increased the cytoplasmic @entity4851 and nuclear @entity8889 content. Zerumbone enhanced the radiosensitivity of @entity19702 -overexpressed U373MG and U87MG cells. In conclusion, overexpression of @entity19702 preferentially sensitized @entity1 @entity463 cells possessing wild type @entity876 to radiation therapy. Blocking of @entity4851 signaling may enhance radiosensitivity independently of the expression of @entity876 and @entity19702 . The crosstalk between @entity4851 signaling and @entity19702 expression in @entity1 @entity463 warrants further investigation.
