Antiproliferative Effect of NS-398, a Cyclooxygenase-2 Inhibitor, in Pancreatic Cancer Cell Lines
Korean Journal of Hepato-Biliary-Pancreatic Surgery
; : 10-20, 2006.
Article
in Ko
| WPRIM
| ID: wpr-112623
Responsible library:
WPRO
ABSTRACT
PURPOSE:
Selective cyclooxygenase (COX)-2 inhibitors have been reported to inhibit cancer cell proliferation. We investigated the effects of NS-398, a selective COX-2 inhibitor, on cell proliferation in human pancreatic cancer cell lines.METHODS:
Human pancreatic cancer cell lines, Aspc-1, Capan-1, and Capan-2 were used. We used western blot and/or RT-PCR to evaluate COX-2 and vascular endothelial growth factor expression. Antiproliferative effects were measured by MTT assay, apoptosis assay and cell cycle analysis. Epidermal growth factor (EGF) and troglitazone were used for combined treatment.RESULTS:
COX-2 was relatively overexpressed in Capan-1 and Capan- 2, but minimal in Aspc-1 cell line. COX-2 mRNA expression was upregulated by 50 microM of NS-398 in Aspc-1 cell line but was downregulated at 100 microM in all cell lines. Treatment with NS-398 increased cell population of G0/G1 phase and also induced early apoptotic changes in a dose-dependent manner in all three cell lines. Combined treatment with EGF or troglitazone did not seem to affect antiproliferative effects of NS-398. All three cell lines expressed vascular endothelial growth factor constitutively and its expression was downregulated by treatment with NS-398. Pretreatment with NS-398 prior to radiation exposure increased radiosensitivity in Capan-2 cells.CONCLUSION:
COX-2 expression was variable in pancreatic cancer cell lines. NS-398 inhibited pancreatic cancer cell proliferation by inducing apoptosis and cell cycle arrest in a dose-dependent manner. Treatment with NS-398 also inhibited expression of VEGF and enhanced radiosensitivity in pancreatic cancer cell lines. COX-2 inhibitors might be promising potential therapeutic agents for patients with pancreatic cancer.Key words
Full text:
1
Index:
WPRIM
Main subject:
Pancreatic Neoplasms
/
Radiation Tolerance
/
RNA, Messenger
/
Cell Cycle
/
Cell Line
/
Blotting, Western
/
Prostaglandin-Endoperoxide Synthases
/
Apoptosis
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Vascular Endothelial Growth Factor A
/
Cell Proliferation
Limits:
Humans
Language:
Ko
Journal:
Korean Journal of Hepato-Biliary-Pancreatic Surgery
Year:
2006
Type:
Article