@entity5 effects and pharmacokinetic application of XXXX .

@entity16771 @entity1 @entity5 @entity3544 @entity5962 @entity8985 @entity3963 @entity876 @entity72373 @entity1435 @entity694
UNASSIGNED: @entity72373 ( @entity16771 ) induced growth inhibition in @entity1 @entity5 cells using the national @entity5 institute (NCI) anticancer drug screen. In our previous study, we demonstrated that @entity16771 exerted growth inhibitory activities in the three @entity1 @entity694 cell lines (Colo 205, HT-29, and HCT-15). To identify the detailed mechanism, we examined the functional importance of @entity3544 and @entity876 in @entity16771 -induced anticancer effect. We used three isogenic @entity694 cell lines, HCT-116, HCT-116 @entity876 (-/-), and HCT-116 @entity3544 (-/-), to evaluate the roles of @entity3544 and @entity876 in the in vitro anticancer effects of @entity16771 . @entity16771 dose-dependently inhibited cell growth, cell migration and increased cell cycle at the G0/G1 phase in HCT116 cells but not in @entity3544 (-/-) and @entity876 (-/-) isogenic HCT-116 cells. Additionally, Western blot showed that @entity16771 treatment induced the @entity3544 , @entity876 , and cyclin-E protein expressions in HCT-116 cells. The @entity3544 associated cell cycle regulatory protein such as cyclin D, @entity8985 , and pRb were decreased after @entity16771 treatment in HCT-116 cells. @entity16771 decreased cell migration in HCT-116 and HCT-116 @entity876 (-/-) but not in HCT-116 @entity3544 (-/-) cells. We observed the up-regulation of @entity5962 , p- @entity1435 , and p- @entity3963 in @entity16771 -treated HCT-116 group but not in HCT-116 @entity3544 (-/-) and HCT-116 @entity876 (-/-) groups. We assumed that @entity3544 was required for @entity16771 -induced anti- @entity694 effect through the @entity3963 and @entity1435 pathway leading to cell cycle arrest and inhibition of cell motility. Mean (   SE) pharmacokinetic parameters of the @entity16771 were as follows: AUC = 64.44    8.41, Cmax = 1.56    0.48 and t1/2 = 113.92    58.19. The pharmacokinetic data suggest @entity16771 can be applied to further clinical study. This is the first pharmacokinetic study of @entity16771 , and indicated that anti-proliferation and the cell mobility inhibition effects of @entity16771 in HCT116 WT cells may result from the induction of @entity3544 through activation of @entity3963 and @entity1435 pathway.
