Journal
CANCER LETTERS
Volume 275, Issue 2, Pages 247-255Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2008.10.023
Keywords
Pancreatic cancer; Cyclooxygenase-2; Peroxisome proliferators-activated receptor; gamma; Proliferation; Apoptosis
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Funding
- Health Bureau of Jiangsu Province, PR China [RC2003118]
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Although inhibition of cyclooxygenase-2 (COX-2) or activation of peroxisome proliferators-activated receptor gamma (PPAR-gamma) leads to growth inhibition in malignancies, the synergistic anti-tumor effects of combination of COX-2 inhibitor (NS-398) and PPAR-gamma agonist (rosiglitazone) on the human pancreatic cancer cells remains unknown. Here, we evaluated the effects of NS-398 and/or rosiglitazone on the cell proliferation and apoptosis in a pancreatic cancer cell line, SW1990. NS-398 and rosiglitazone decreased cell proliferation in a dose- and time-dependent manner. Proliferating cell nuclear antigen (PCNA) labeling index significantly decreased in the cells treated with either NS-398 or rosiglitazone. Both NS-398 and rosiglitazone alone induced apoptotic cell death of SW1990. The combination of NS-398 and rosiglitazone exerted synergistic effects on proliferation inhibition, and apoptosis induction in SW1990 cells. with down-regulation of Bcl-2 and up-regulation of Bax expression. Our results indicate that simultaneous targeting of COX-2 and PPAR-gamma inhibits pancreatic cancer development more effectively than targeting each molecule alone. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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