Gene modulation by @entity9859 and @entity2247 specific inhibitors in @entity1 XXXX cells.

@entity1 @entity18429 @entity25592 @entity12985 @entity9322 @entity16539 @entity23390 @entity23638 @entity14 @entity9859 @entity2247 @entity3287 @entity26112
@entity9859 and @entity2247 specific inhibitors exert chemo-preventative activity. However, the exact mechanisms for this activity remain unclear. Increasing evidence suggests that non-steroidal anti-inflammatory drugs regulate gene expression, which may be responsible, in part, for this activity. In this study, @entity1 @entity14 HCT-116 cells were treated with the @entity9859 specific inhibitor @entity16539 and the @entity2247 specific inhibitor @entity25592 to evaluate their ability to induce apoptosis, inhibit cell proliferation, inhibit growth on soft agar and modulate gene expression. The @entity9859 specific inhibitor, @entity16539 significantly induced apoptosis and inhibited the growth of HCT-116 cells on soft agar, an in vitro assay for tumorigenicity. @entity25592 moderately induced apoptosis and inhibited growth on soft agar at higher concentrations than were required for @entity16539 . Previously, we reported that the potent chemo-preventative drug sulindac @entity3287 altered the expression of eight genes including several transcription factors that may be linked to this drug's chemo-preventative activity. HCT-116 cells were treated with various concentrations of @entity16539 or @entity25592 and changes in the expression of these eight genes were determined by real-time reverse transcription- polymerase chain reaction. @entity16539 modulated mRNA expression of the eight genes studied. In contrast, @entity25592 required approximately 5-10-fold higher concentrations to achieve similar degrees of gene modulation in six of eight genes. Changes in protein expression by @entity16539 also occurred for five of these genes with antibodies available ( @entity23390 , @entity23638 , @entity9322 , @entity26112 and @entity18429 ). In conclusion, this is the first report to suggest that like @entity12985 , the @entity9859 specific inhibitor @entity16539 appears to elicit chemo-preventative activity by altering gene expression, while the chemo-preventative effects of @entity25592 are complex and probably work through these and other mechanisms, such as the inhibition of @entity2247 .
