Autocrine vascular endothelial growth factor/vascular endothelial growth factor receptor-2 growth pathway represents a cyclooxygenase-2-independent target for the cyclooxygenase-2 inhibitor NS-398 in colon cancer cells

Jin Kim Seok, Jae Hong Seo, Jung Lee Yoo, Hye Yoon Ji, Chul Won Choi, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim

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19 Citations (Scopus)

Abstract

Objectives: Coexpression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) has been reported in tumor cells, suggesting the presence of an autocrine VEGF/VEGFR-2 growth pathway in solid tumors. Thus, we hypothesize that the presence of this autocrine pathway in colon cancer cells may be a COX-2-independent target of COX-2 inhibitors and a mechanism behind the antitumor effects of these agents. Methods: COX-2-positive (Caco2, HT-29) and COX-2-negative colon cancer cells (DLD-1, Hct-15) were used. Expression of VEGFR-2 was evaluated by Western blot and reverse transcriptase-polymerase chain reaction and VEGF production was measured from culture supernatant by enzyme-linked immunosorbent assay. Growth inhibition and the expression of VEGF and VEGFR-2 were compared after treatment with the COX-2 inhibitor, NS-398 at doses ranging from 5 to 100 μM. Results: VEGF and VEGFR-2 were expressed in all four colon cancer cells and a blockade of VEGFR-2 with anti-VEGFR-2 antibody treatment induced growth inhibition of colon cancer cells, supporting the presence of autocrine VEGF/VEGFR-2 growth pathway. NS-398 suppressed the growth of colon cancer cells, independent of COX-2 expression. VEGFR-2 expression of tumor cells was reduced after NS-398 treatment at 100 μM, the concentration at which maximal growth inhibition was induced. The amount of VEGF in culture supernatant was increased by NS-398 at 100 μM, suggesting increased secretion of VEGF in compensation for reduced VEGFR-2 expression. Conclusion: The autocrine VEGF/VEGFR-2 growth pathway could be a COX-2-independent target of the COX-2 inhibitor, NS-398, in colon cancer cells.

Original languageEnglish
Pages (from-to)204-211
Number of pages8
JournalOncology
Volume68
Issue number2-3
DOIs
Publication statusPublished - 2005 Jul 1

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Vascular Endothelial Growth Factor Receptor-2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase 2
Colonic Neoplasms
Vascular Endothelial Growth Factor A
Growth
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
Neoplasms
Reverse Transcriptase Polymerase Chain Reaction
Antineoplastic Agents
Therapeutics
Western Blotting
Enzyme-Linked Immunosorbent Assay

Keywords

  • Colon cancer cell
  • Cyclooxygenase-2 inhibitor
  • Cyclooxygenase-2-independent target
  • VEGF/VEGFR-2 growth pathway, autocrine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{502234fa6e1e432bad6277400c4f1bc7,
title = "Autocrine vascular endothelial growth factor/vascular endothelial growth factor receptor-2 growth pathway represents a cyclooxygenase-2-independent target for the cyclooxygenase-2 inhibitor NS-398 in colon cancer cells",
abstract = "Objectives: Coexpression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) has been reported in tumor cells, suggesting the presence of an autocrine VEGF/VEGFR-2 growth pathway in solid tumors. Thus, we hypothesize that the presence of this autocrine pathway in colon cancer cells may be a COX-2-independent target of COX-2 inhibitors and a mechanism behind the antitumor effects of these agents. Methods: COX-2-positive (Caco2, HT-29) and COX-2-negative colon cancer cells (DLD-1, Hct-15) were used. Expression of VEGFR-2 was evaluated by Western blot and reverse transcriptase-polymerase chain reaction and VEGF production was measured from culture supernatant by enzyme-linked immunosorbent assay. Growth inhibition and the expression of VEGF and VEGFR-2 were compared after treatment with the COX-2 inhibitor, NS-398 at doses ranging from 5 to 100 μM. Results: VEGF and VEGFR-2 were expressed in all four colon cancer cells and a blockade of VEGFR-2 with anti-VEGFR-2 antibody treatment induced growth inhibition of colon cancer cells, supporting the presence of autocrine VEGF/VEGFR-2 growth pathway. NS-398 suppressed the growth of colon cancer cells, independent of COX-2 expression. VEGFR-2 expression of tumor cells was reduced after NS-398 treatment at 100 μM, the concentration at which maximal growth inhibition was induced. The amount of VEGF in culture supernatant was increased by NS-398 at 100 μM, suggesting increased secretion of VEGF in compensation for reduced VEGFR-2 expression. Conclusion: The autocrine VEGF/VEGFR-2 growth pathway could be a COX-2-independent target of the COX-2 inhibitor, NS-398, in colon cancer cells.",
keywords = "Colon cancer cell, Cyclooxygenase-2 inhibitor, Cyclooxygenase-2-independent target, VEGF/VEGFR-2 growth pathway, autocrine",
author = "Seok, {Jin Kim} and Seo, {Jae Hong} and Yoo, {Jung Lee} and Ji, {Hye Yoon} and Choi, {Chul Won} and Kim, {Byung Soo} and Shin, {Sang Won} and Kim, {Yeul Hong} and Kim, {Jun Suk}",
year = "2005",
month = "7",
day = "1",
doi = "10.1159/000086775",
language = "English",
volume = "68",
pages = "204--211",
journal = "Oncology",
issn = "0030-2414",
publisher = "UBM Medica Healthcare Publications",
number = "2-3",

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TY - JOUR

T1 - Autocrine vascular endothelial growth factor/vascular endothelial growth factor receptor-2 growth pathway represents a cyclooxygenase-2-independent target for the cyclooxygenase-2 inhibitor NS-398 in colon cancer cells

AU - Seok, Jin Kim

AU - Seo, Jae Hong

AU - Yoo, Jung Lee

AU - Ji, Hye Yoon

AU - Choi, Chul Won

AU - Kim, Byung Soo

AU - Shin, Sang Won

AU - Kim, Yeul Hong

AU - Kim, Jun Suk

PY - 2005/7/1

Y1 - 2005/7/1

N2 - Objectives: Coexpression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) has been reported in tumor cells, suggesting the presence of an autocrine VEGF/VEGFR-2 growth pathway in solid tumors. Thus, we hypothesize that the presence of this autocrine pathway in colon cancer cells may be a COX-2-independent target of COX-2 inhibitors and a mechanism behind the antitumor effects of these agents. Methods: COX-2-positive (Caco2, HT-29) and COX-2-negative colon cancer cells (DLD-1, Hct-15) were used. Expression of VEGFR-2 was evaluated by Western blot and reverse transcriptase-polymerase chain reaction and VEGF production was measured from culture supernatant by enzyme-linked immunosorbent assay. Growth inhibition and the expression of VEGF and VEGFR-2 were compared after treatment with the COX-2 inhibitor, NS-398 at doses ranging from 5 to 100 μM. Results: VEGF and VEGFR-2 were expressed in all four colon cancer cells and a blockade of VEGFR-2 with anti-VEGFR-2 antibody treatment induced growth inhibition of colon cancer cells, supporting the presence of autocrine VEGF/VEGFR-2 growth pathway. NS-398 suppressed the growth of colon cancer cells, independent of COX-2 expression. VEGFR-2 expression of tumor cells was reduced after NS-398 treatment at 100 μM, the concentration at which maximal growth inhibition was induced. The amount of VEGF in culture supernatant was increased by NS-398 at 100 μM, suggesting increased secretion of VEGF in compensation for reduced VEGFR-2 expression. Conclusion: The autocrine VEGF/VEGFR-2 growth pathway could be a COX-2-independent target of the COX-2 inhibitor, NS-398, in colon cancer cells.

AB - Objectives: Coexpression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) has been reported in tumor cells, suggesting the presence of an autocrine VEGF/VEGFR-2 growth pathway in solid tumors. Thus, we hypothesize that the presence of this autocrine pathway in colon cancer cells may be a COX-2-independent target of COX-2 inhibitors and a mechanism behind the antitumor effects of these agents. Methods: COX-2-positive (Caco2, HT-29) and COX-2-negative colon cancer cells (DLD-1, Hct-15) were used. Expression of VEGFR-2 was evaluated by Western blot and reverse transcriptase-polymerase chain reaction and VEGF production was measured from culture supernatant by enzyme-linked immunosorbent assay. Growth inhibition and the expression of VEGF and VEGFR-2 were compared after treatment with the COX-2 inhibitor, NS-398 at doses ranging from 5 to 100 μM. Results: VEGF and VEGFR-2 were expressed in all four colon cancer cells and a blockade of VEGFR-2 with anti-VEGFR-2 antibody treatment induced growth inhibition of colon cancer cells, supporting the presence of autocrine VEGF/VEGFR-2 growth pathway. NS-398 suppressed the growth of colon cancer cells, independent of COX-2 expression. VEGFR-2 expression of tumor cells was reduced after NS-398 treatment at 100 μM, the concentration at which maximal growth inhibition was induced. The amount of VEGF in culture supernatant was increased by NS-398 at 100 μM, suggesting increased secretion of VEGF in compensation for reduced VEGFR-2 expression. Conclusion: The autocrine VEGF/VEGFR-2 growth pathway could be a COX-2-independent target of the COX-2 inhibitor, NS-398, in colon cancer cells.

KW - Colon cancer cell

KW - Cyclooxygenase-2 inhibitor

KW - Cyclooxygenase-2-independent target

KW - VEGF/VEGFR-2 growth pathway, autocrine

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