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KMID : 0371320110810020115
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Journal of the Korean Surgical Society
2011 Volume.81 No. 2 p.115 ~ p.121
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Up-regulation of cyclooxygenase-2-derived prostaglandin E2 in colon cancer cells resistant to 5-fluorouracil
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Choi Cheol-Hee
Lee Tae-Bum
Lee Yeon-Ah
Kim Kyung-Jong
Choi Suk
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Abstract
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Purpose: It has been suggested that constitutive up-regulation of cyclooxygenase (COX)-2 is associated with resistance to apoptosis, increased angiogenesis, and increased tumor invasiveness in various cancers including colon cancer. There are many factors involved in the resistance to 5-fluorouracil (5-FU) in colon cancer. However, little is known about the role of COX-2 in acquired resistance to 5-FU in colon cancer.
Methods: Hence we investigated whether COX-2 contribute to acquired resistance to 5-FU in colon cancer cells, using cytotoxicity assay for cell survival, reverse transcription-polymerase chain reaction (RT-PCR) for vascular endothelial growth factor (VEGF), quantitative RT-PCR for COX-1 and COX-2, and enzyme-linked immunosorbent assay for PGE2.
Results: The 5-FU resistant colon cancer cells, SNU-C5/5FUR, showed increased expression of COX-2, prostaglandin E2 (PGE2), and VEGF, compared to its parental cell (SNU-C5). By treatment with meloxicam, the expression of PGE2 and VEGF was reduced significantly in the resistant cells, but not in the parent cells.
Conclusion: These results demonstrate that COX-2 derived PGE2 is up-regulated and COX-2 inhibitor may have an anti-angiogenic effect in the colon cancer cells resistant to 5-FU.
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KEYWORD
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Cyclooxygenase-2, Prostaglandin E2, 5-Fluorouracil, Acquired resistance, Colon neoplasms
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