´ëÀå¾Ï ¼¼Æ÷¿¡¼ 5-FUÀÇ ¼¼Æ÷µ¶¼º¿¡ ´ëÇÑ NSAIDsÀÇ º¸Á¶ÀûÀÎ È¿°ú
Adjuvant Effect of NSAIDs on the Cytotoxicity of Colon Cancer Cells to 5-FU
ÀÌŹü, ±è°æÁ¾, ¹Î¿µµ·, °¼ºÀÎ, Á¤±ÇÀ², ÀÌÀç¾÷, ÃÖöÈñ,
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ÀÌŹü ( Lee Tae-Bum )
Á¶¼±´ëÇб³ ÀÇ°ú´ëÇÐ ³»¼º¼¼Æ÷¿¬±¸¼¾ÅÍ
±è°æÁ¾ ( Kim Kyung-Jong )
Á¶¼±´ëÇб³ ÀÇ°ú´ëÇÐ ¿Ü°úÇб³½Ç
¹Î¿µµ· ( Min Young-Don )
Á¶¼±´ëÇб³ ÀÇ°ú´ëÇÐ ¿Ü°úÇб³½Ç
°¼ºÀÎ ( Kang Sung-In )
Á¶¼±´ëÇб³ ÀÇ°ú´ëÇÐ ¾à¸®Çб³½Ç
Á¤±ÇÀ² ( Jung Kwon-Ryul )
Á¶¼±´ëÇб³ ÀÇ°ú´ëÇÐ ¾à¸®Çб³½Ç
ÀÌÀç¾÷ ( Lee Jae-Up )
Á¶¼±´ëÇб³ ÀÇ°ú´ëÇÐ ¾à¸®Çб³½Ç
ÃÖöÈñ ( Choi Cheol-Hee )
Á¶¼±´ëÇб³ ÀÇ°ú´ëÇÐ ³»¼º¼¼Æ÷¿¬±¸¼¾ÅÍ
KMID : 0356720050210030121
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. J Korean Soc Coloproctol 2005;21: 121-128
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COX-2;NSAIDs;5-FU;Additive effect;Colon cancer cells COX-2
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