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Antimetastatic activity of a cyclooxygenase-2 inhibitor

Cyclooxygenase-2 (COX-2) expression is increased in breast cancer and surgery has been shown to increase the growth of metastatic tumours. We investigated the effect of selective COX-2 inhibition on the growth of metastases in either an experimental metastasis model or following excision of a murine...

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Autores principales: Roche-Nagle, G, Connolly, E M, Eng, M, Bouchier-Hayes, D J, Harmey, J H
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409822/
https://www.ncbi.nlm.nih.gov/pubmed/15213717
http://dx.doi.org/10.1038/sj.bjc.6601967
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author Roche-Nagle, G
Connolly, E M
Eng, M
Bouchier-Hayes, D J
Harmey, J H
author_facet Roche-Nagle, G
Connolly, E M
Eng, M
Bouchier-Hayes, D J
Harmey, J H
author_sort Roche-Nagle, G
collection PubMed
description Cyclooxygenase-2 (COX-2) expression is increased in breast cancer and surgery has been shown to increase the growth of metastatic tumours. We investigated the effect of selective COX-2 inhibition on the growth of metastases in either an experimental metastasis model or following excision of a murine primary breast tumour. 50 000 4T1 mammary carcinoma cells were injected into the mammary fat pad of female BALB/c mice. When the mean TD reached 8±0.4 mm, tumours were excised and the mice were randomised into two groups (n=12 per group) to receive daily intraperitoneal injections of the selective COX-2 inhibitor, SC-236 or drug vehicle for 14 days. Alternatively, experimental metastases were established by tail-vein injection of 50 000 4T1 cells. Mice received either the selective COX-2 inhibitor, SC-236 or drug vehicle for 14 days (n=12 per group). SC-236 treatment significantly reduced tumour burden, the number and size of spontaneous metastases following primary tumour excision. SC-236 treatment also reduced tumour burden, the number and size of experimental metastases. Immunohistochemical staining demonstrated that COX-2 inhibition reduced microvessel density and increased apoptosis within both spontaneous and experimental metastases. These data clearly demonstrate that the selective COX-2 inhibitor, SC-236, has potent antimetastatic activity against both spontaneous metastases arising following primary tumour excision and experimental metastases.
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spelling pubmed-24098222009-09-10 Antimetastatic activity of a cyclooxygenase-2 inhibitor Roche-Nagle, G Connolly, E M Eng, M Bouchier-Hayes, D J Harmey, J H Br J Cancer Experimental Therapeutics Cyclooxygenase-2 (COX-2) expression is increased in breast cancer and surgery has been shown to increase the growth of metastatic tumours. We investigated the effect of selective COX-2 inhibition on the growth of metastases in either an experimental metastasis model or following excision of a murine primary breast tumour. 50 000 4T1 mammary carcinoma cells were injected into the mammary fat pad of female BALB/c mice. When the mean TD reached 8±0.4 mm, tumours were excised and the mice were randomised into two groups (n=12 per group) to receive daily intraperitoneal injections of the selective COX-2 inhibitor, SC-236 or drug vehicle for 14 days. Alternatively, experimental metastases were established by tail-vein injection of 50 000 4T1 cells. Mice received either the selective COX-2 inhibitor, SC-236 or drug vehicle for 14 days (n=12 per group). SC-236 treatment significantly reduced tumour burden, the number and size of spontaneous metastases following primary tumour excision. SC-236 treatment also reduced tumour burden, the number and size of experimental metastases. Immunohistochemical staining demonstrated that COX-2 inhibition reduced microvessel density and increased apoptosis within both spontaneous and experimental metastases. These data clearly demonstrate that the selective COX-2 inhibitor, SC-236, has potent antimetastatic activity against both spontaneous metastases arising following primary tumour excision and experimental metastases. Nature Publishing Group 2004-07-19 2004-06-22 /pmc/articles/PMC2409822/ /pubmed/15213717 http://dx.doi.org/10.1038/sj.bjc.6601967 Text en Copyright © 2004 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Experimental Therapeutics
Roche-Nagle, G
Connolly, E M
Eng, M
Bouchier-Hayes, D J
Harmey, J H
Antimetastatic activity of a cyclooxygenase-2 inhibitor
title Antimetastatic activity of a cyclooxygenase-2 inhibitor
title_full Antimetastatic activity of a cyclooxygenase-2 inhibitor
title_fullStr Antimetastatic activity of a cyclooxygenase-2 inhibitor
title_full_unstemmed Antimetastatic activity of a cyclooxygenase-2 inhibitor
title_short Antimetastatic activity of a cyclooxygenase-2 inhibitor
title_sort antimetastatic activity of a cyclooxygenase-2 inhibitor
topic Experimental Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409822/
https://www.ncbi.nlm.nih.gov/pubmed/15213717
http://dx.doi.org/10.1038/sj.bjc.6601967
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