For the best of our knowledge, this is actually the first report of celecoxib inhibition of GSK3. In addition to Akt, other kinases including p70S6K and PKC can also phosphorylate GSK3. Within our study, we didn’t demonstrate a role for mTOR/p70S6K in celecoxibinduced GSK phosphorylation GW9508 since rapamycin efficiently inhibited the basal amounts of p S6, but didn’t avoid the upsurge in Akt phosphorylation by celecoxib. Nevertheless, both Kiminas 31 8220 and GF109203X, which are PKC pan inhibitors, abolished celecoxibinduced GSK3 phosphorylation, suggesting that celecoxib induces PKC dependent GSK3 phosphorylation or inhibition. It is recognized that PKC includes multiple isoforms. Among these isoforms, PKC, T or isoforms have been proposed to control GSK3 phosphorylation. In our study, we discovered that both G 6983, a specific PKC inhibitor missing activity from the u isoform, and G 6979, a specific PKC /B inhibitor, however not Rottlerin, a specific PKC inhibitor, were as powerful Skin infection while the PKC pan inhibitors in abolishing celecoxib induced GSK3 phosphorylation. Ergo, we declare that the PKC /B isoforms could be essential for mediating celecoxib induced phosphorylation. These findings warrant further study toward this direction. Our finding on activation of PKC is fresh though we’ve yet to determine the system through which celecoxib activates PKC, warranting the further investigation with this subject. It has been shown that GSK3B inhibition with either small molecule inhibitors or siRNAs potentiates TRAIL induced apoptosis in human prostate cancer cells. But, the underlying mechanisms are as yet not known. Within our study, we’re able to reproduce this biological phenomenon in human NSCLC cells. Really essentially, we observed that inhibition pifithrin of GSK3 with either siRNAs or small molecule inhibitors downregulated c FLIP levels, clearly indicating that GSK3 inhibition in downregulation of c FLIP levels. Complementarily, forced expression of CA GSK3 improved d FLIP levels. Hence, our findings demonstrably show that GSK3 adjusts c FLIP degrees. To the best of our knowledge, this is actually the first review demonstrating GSK3 dependent regulation of c FLIP. Provided that enforced expression of ectopic c FLIP expression protects cells from induction of apoptosis induced by GSK inhibition plus TRAIL, it’s plausible to conclude that c FLIP downregulation ought to be an important function accounting for GSK3 inhibition mediated enhancement of TRAIL induced apoptosis. Hence, our findings on GSK3 regulation of c FLIP provide a reasonable mechanism where GSK inhibition potentiates TRAIL induced apoptosis. It’s known that c FLIP, including FLIPL and FLIPS, are proteins subjected to rapid turnover managed through ubiquitin/proteasome mediated protein degradation.