Up-regulation of cyclooxygenase-2-derived prostaglandin E2 in colon cancer cells resistant to 5-fluorouracil / 대한외과학회지

ABSTRACT

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.