The selective cyclooxygenase-2 inhibitor nimesulide induces apoptosis in pancreatic cancer cells independent of COX-2
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2003 |
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| Erschienen: |
2003 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
Pancreas - 26(2003), 1 vom: 27. Jan., Seite 33-41 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Eibl, Guido [VerfasserIn] |
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| Anmerkungen: |
Date Completed 08.01.2003 Date Revised 06.09.2019 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM122830989 |
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| 100 | 1 | |a Eibl, Guido |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The selective cyclooxygenase-2 inhibitor nimesulide induces apoptosis in pancreatic cancer cells independent of COX-2 |
| 264 | 1 | |c 2003 | |
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| 500 | |a Date Completed 08.01.2003 | ||
| 500 | |a Date Revised 06.09.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Wente, Moritz N |e verfasserin |4 aut | |
| 700 | 1 | |a Hines, Oscar J |e verfasserin |4 aut | |
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