Up-regulation of cyclooxygenase-2-derived prostaglandin E₂in colon cancer cells resistant to 5-fluorouracil

Abstract

PurposeIt 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.MethodsHence 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.ResultsThe 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.ConclusionThese 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.

A Long Non-Coding RNA snaR Contributes to 5-Fluorouracil Resistance in Human Colon Cancer Cells

“…Two 5-FU-resistant SNU-C4R and SNU-C5R cell lines were previously established from human colon cancer cells, SNU-C4 and SNU-C5, respectively (Choi et al, 2011;Jung et al, 2007;Shin et al, 2005;. We confirmed the relative chemosensitivity of these resistant cell lines against 5-FU using MTT assay.…”

“…The human colon cancer cell lines SNU-C4 and SNU-C5 (Oh et al, 1999;Park et al, 1987), and their individual 5-FU-resistant cell lines, SNU-C4R and SNU-C5R, were obtained from the Korean Cell Line Bank (Korea) (Choi et al, 2011;Shin et al, 2005;. SNU-C4, SNU-C5, and HCT-116 cells were maintained in RPMI medium (Thermo Scientific Inc.) supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin.…”

Tandutinib Inhibits the Akt/mTOR Signaling Pathway to Inhibit Colon Cancer Growth

“…Tandutinib treatment seems to mediate its actions through multiple molecular targets, including COX-2. Given the high levels of resistance to apoptosis due to COX-2 overexpression (42, 43), treating cells with Tandutinib could potentially restore apoptotic susceptibility of colon cancer cells in part through the downregulation of this gene.…”

New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis

“…1, COX-2 induces chemokine (C-X-C motif) ligand 2 (CXCL-2) and VEGF to promote angiogenesis to facilitate tumor growth. Indeed, evidence for the existence of a COX-2-VEGF inductive partnership in CRC can be gained from studies examining the effect of COX-2-specific inhibitors, where COX-2 inhibition in CRC cell lines and tumors in vivo has been shown to directly reduce VEGF expression [55][56][57][58]. Taken together, these findings suggest that the COX-2-VEGF inductive axis contributes to tumor cell growth and metastasis via the pro-angiogenic and lymphangiogenic effects of VEGF, providing for both the oxygenation demands of the growing tumor and the means through which the tumor cells can metastasize.…”