Antiproliferative Effect of NS-398, a Cyclooxygenase-2 Inhibitor, in Pancreatic Cancer Cell Lines..
- Author:
Hyun Dong LEE
1
;
Jin Woo PARK
;
Jae Woon CHOI
;
Hoon KANG
;
Guang Bi JIN
;
Su Mun CHOI
;
Sung Su PARK
;
Lee Chan JANG
Author Information
1. Department of Surgery, Chungbuk National University Medical School, Korea. jwchoi@chungbuk.ac.kr
- Publication Type:Original Article
- Keywords:
Cyclooxygenase-2;
NS-398;
Antiproliferation;
Apoptosis;
VEGF;
Radiosensitivity
- MeSH:
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
- From:Korean Journal of Hepato-Biliary-Pancreatic Surgery
2006;10(1):10-20
- CountryRepublic of Korea
- Language:Korean
-
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.
