Adjuvant Effect of NSAIDs on the Cytotoxicity of Colon Cancer Cells to 5-FU.
- Author:
Tae Bum LEE
1
;
Kyung Jong KIM
;
Young Don MIN
;
Sung In KANG
;
Kwon Ryul JUNG
;
Jae Up LEE
;
Cheol Hee CHOI
Author Information
1. Department of Surgery, College of Medicine, Chosun University, Gwangju, Korea. kjkim@chosun.ac.kr
- Publication Type:Original Article
- Keywords:
COX-2;
NSAIDs;
5-FU;
Additive effect;
Colon cancer cells
- MeSH:
Anti-Inflammatory Agents, Non-Steroidal*;
Arachidonic Acid;
Aspirin;
Blotting, Western;
Carcinogenesis;
Cell Line;
Colon*;
Colonic Neoplasms*;
Colorectal Neoplasms;
Cyclooxygenase 2 Inhibitors;
Fluorouracil*;
Prostaglandin-Endoperoxide Synthases;
Prostaglandins;
RNA, Messenger
- From:Journal of the Korean Society of Coloproctology
2005;21(3):121-128
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: Cyclooxygenase (COX)-2, an inducible enzyme that catalyzes the conversion of arachidonic acid to prostaglandins, is believed to be an important enzyme related to colorectal cancer. A large number of studies have supported the concept that non-steroidal anti-inflammatory drugs (NSAIDs) targeting COX alter the biologic processes of colon carcinogenesis. Although COX-2 inhibitors generally reduce the growth rate of established tumors, tumor regression is rarely observed. Hence, it is reasonable that COX-2 inhibitors be given in conjunction with standard anti-cancer therapy in treating cancer. We investigated whether aspirin and meloxicam not only are cytotoxic but also potentiate the antitumor effect of 5-Fluorouracil (5-FU) against colon cancer cells. METHODS: Expressions of COX-1 and COX-2 were determined by using the reverse transcriptase-polymerase chain reaction (RT-PCR) & Western blotting assay in 9 colon cancer cell lines. The cytotoxicities of NSAIDs and/or 5-FU were determined by using a microculture tetrazolium dye (MTT) assay. RESULTS: COX-1 mRNA and protein, as well as COX-2 mRNA, were variably expressed in all the cell lines tested whereas COX-2 protein was expressed in HT-29 and to a lesser extent in HCT-8, but not in the other cell lines. We selected two representative cell lines, HT-29 expressing COX-2 protein and SNU-C1 not expressing it. The dose-dependent cytotoxicity was observed in both cell lines treated with aspirin and with meloxicam. A combination treatment of aspirin or meloxicam with 5-FU revealed some additive effect, rather than a synergistic effect, for both cells lines. This additive effect was remarkable even for low concentrations of the drugs. Furthermore, the additive effect was highest when the combination was adminstered sequentially, 5-FU followed by aspirin or meloxicam, in both cell lines. CONCLUSIONS: These results suggest that a combination therapy using NSAIDs and 5-FU might be useful in the treatment of colon cancer cells not expressing COX-2, as well as in colon cancer cells expressing COX-2.
