Korean J Hepatobiliary Pancreat Surg.  2006 Mar;10(1):10-20.

Antiproliferative Effect of NS-398, a Cyclooxygenase-2 Inhibitor, in Pancreatic Cancer Cell Lines.

• Lee HD
• Park JW
• Choi JW
• Kang H
• Jin GB
• Choi SM
• Park SS
• Jang LC

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.

Keyword

Cyclooxygenase-2; NS-398; Antiproliferation; Apoptosis; VEGF; Radiosensitivity

MeSH Terms

Apoptosis
Blotting, Western
Cell Cycle
Cell Cycle Checkpoints
Cell Line*
Cell Proliferation
Cyclooxygenase 2 Inhibitors
Cyclooxygenase 2*
Epidermal Growth Factor
Humans
Pancreatic Neoplasms*
Prostaglandin-Endoperoxide Synthases
Radiation Tolerance
RNA, Messenger
Vascular Endothelial Growth Factor A
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Epidermal Growth Factor
Prostaglandin-Endoperoxide Synthases
RNA, Messenger
Vascular Endothelial Growth Factor A