INTRODUCTION: Selective cyclooxygenase-2 (COX-2) inhibition reduces the growth of many cancer cell lines, and this effect may be mediated through induction of apoptosis. This study was designed to investigate the effects of the COX-2 inhibitor nimesulide on the growth of human pancreatic cancer cells. METHODOLOGY: Reverse transcriptase-polymerase chain reaction analysis, northern blotting, and immunoblotting were used to demonstrate COX-2 mRNA and protein in two pancreatic cancer cell lines: BxPC-3 and MIA PaCa-2. The effect of nimesulide on cell growth was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and cell count. Apoptosis was determined by FACS analysis, DNA laddering, and assessment of the floating cell/attached cell ratio. Caspase-3 activation was evaluated by measuring caspase-3 cellular activity and by determining the effects of two caspase inhibitors on cell viability. RESULTS: COX-2 mRNA was detected in both cell lines. Immunoblotting confirmed COX-2 protein expression in only the BxPC-3 cell line. Nimesulide decreased cell viability and inhibited cell growth in both cell lines. Incubation with 100 micromol/L nimesulide increased the fraction of apoptotic cells and the floating cell/attached cell ratio in both cell lines. DNA laddering was observed after incubation with nimesulide for 96 hours. There was no increase in caspase-3 activity within 96 hours. CONCLUSION: The selective COX-2 inhibitor nimesulide is antimitogenic in pancreatic cancer cells, which is independent of COX-2 expression. This effect in part is mediated by the induction of apoptosis.
INTRODUCTION: Selective cyclooxygenase-2 (COX-2) inhibition reduces the growth of many cancer cell lines, and this effect may be mediated through induction of apoptosis. This study was designed to investigate the effects of the COX-2 inhibitor nimesulide on the growth of humanpancreatic cancer cells. METHODOLOGY: Reverse transcriptase-polymerase chain reaction analysis, northern blotting, and immunoblotting were used to demonstrate COX-2 mRNA and protein in two pancreatic cancer cell lines: BxPC-3 and MIA PaCa-2. The effect of nimesulide on cell growth was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and cell count. Apoptosis was determined by FACS analysis, DNA laddering, and assessment of the floating cell/attached cell ratio. Caspase-3 activation was evaluated by measuring caspase-3 cellular activity and by determining the effects of two caspase inhibitors on cell viability. RESULTS:COX-2 mRNA was detected in both cell lines. Immunoblotting confirmed COX-2 protein expression in only the BxPC-3 cell line. Nimesulide decreased cell viability and inhibited cell growth in both cell lines. Incubation with 100 micromol/L nimesulide increased the fraction of apoptotic cells and the floating cell/attached cell ratio in both cell lines. DNA laddering was observed after incubation with nimesulide for 96 hours. There was no increase in caspase-3 activity within 96 hours. CONCLUSION: The selective COX-2 inhibitor nimesulide is antimitogenic in pancreatic cancer cells, which is independent of COX-2 expression. This effect in part is mediated by the induction of apoptosis.
Authors: Guido Eibl; Zobeida Cruz-Monserrate; Murray Korc; Maxim S Petrov; Mark O Goodarzi; William E Fisher; Aida Habtezion; Aurelia Lugea; Stephen J Pandol; Phil A Hart; Dana K Andersen Journal: J Acad Nutr Diet Date: 2017-09-12 Impact factor: 4.910
Authors: Pamela L Crowell; C Max Schmidt; Michele T Yip-Schneider; Jesse J Savage; Dean A Hertzler; William O Cummings Journal: Neoplasia Date: 2006-06 Impact factor: 5.715
Authors: Izumi Ohno; Guido Eibl; Irina Odinokova; Mouad Edderkaoui; Robert D Damoiseaux; Moussa Yazbec; Ravinder Abrol; William A Goddard; Osamu Yokosuka; Stephen J Pandol; Anna S Gukovskaya Journal: Am J Physiol Gastrointest Liver Physiol Date: 2009-09-17 Impact factor: 4.052