Regulation of expression of cd133, a colon cancer stem cell marker and other stemness genes/pathways, by celecoxib: Clues from clinical observations

e15065 Background: CD133 identifies intestinal stem cells and colon CSC, the putative culprit of cancer initiation, progression and resistance. Elevated CD133 levels at protein & mRNA levels predict poor outcomes in patients (pts) with colon cancer. Given that celecoxib reduces colon polyp and only maintenance capecitabine plus celecoxib lead to paradoxically high complete remission (CR) in colon cancer pts who had no resection or positive margin resection of metastases (ASCO 2007), we hypothesized that celecoxib could modulate CD133 and other stemness genes/signaling pathways. Methods: we studied the effects of celecoxib versus 5-FU on CD133, Wnt and other stemness genes/pathways using flow cytometry, immunoflurorescence, real time RT-PCR, western blot, TOP-Flash for Wnt, limiting dilution assay, and Affymetrix in colon cancer cell lines and primary colon cancer spheres. Results: Celecoxib or 5FU inhibited the growth of COX-2+ HT29 or COX-2- DLD1 that express CD133 at 80% and 30% respectively. Only celec...