Cargando…

Nitric Oxide (NO) and Cyclooxygenase-2 (COX-2) Cross-Talk in Co-Cultures of Tumor Spheroids with Normal Cells

Cyclooxygenases (COX), prostaglandin E(2) (PGE(2)) and nitric oxide (NO) are believed to be some of the most important factors related to colon cancer growth and metastasis. In this study, we aimed to investigate the associations between COX-2, PGE(2) and NO in co-cultures of human colon cancer sphe...

Descripción completa

Detalles Bibliográficos
Autores principales: Paduch, Roman, Kandefer-Szerszeń, Martyna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170423/
https://www.ncbi.nlm.nih.gov/pubmed/21909878
http://dx.doi.org/10.1007/s12307-011-0063-x
_version_ 1782211627673714688
author Paduch, Roman
Kandefer-Szerszeń, Martyna
author_facet Paduch, Roman
Kandefer-Szerszeń, Martyna
author_sort Paduch, Roman
collection PubMed
description Cyclooxygenases (COX), prostaglandin E(2) (PGE(2)) and nitric oxide (NO) are believed to be some of the most important factors related to colon cancer growth and metastasis. In this study, we aimed to investigate the associations between COX-2, PGE(2) and NO in co-cultures of human colon cancer spheroids obtained from different tumor grades with normal human colonic epithelium and myofibroblast monolayers. L-arginine (2 mM), a substrate for nitric oxide synthases (NOS), decreased COX-2 and PGE(2) levels, while N(G)-nitro-L-arginine methyl ester (L-NAME) (2 mM), a NOS inhibitor, had no influence on COX-2 and PGE(2) levels but limited tumor cell motility. NS398 (75 μM), a selective COX-2 inhibitor, had no significant influence on NO level but decreased motility of tumor cells. COX-2, PGE(2) and NO levels depended on the tumor grade of the cells, being the highest in Duke’s stage III colon carcinoma. Summing up, we showed that addition of L-arginine at doses which did not stimulate NO level caused a significant decrease in COX-2 and PGE(2) amounts in co-cultures of colon tumor spheroids with normal epithelial cells and myofibroblasts. Any imbalances in NO level caused by exogenous factors influence COX-2 and PGE(2) amounts depending on the kind of cells, their reciprocal interactions and the local microenvironmental conditions. The knowledge of these effects may be useful in limiting colon carcinoma progression and invasion.
format Online
Article
Text
id pubmed-3170423
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Springer Netherlands
record_format MEDLINE/PubMed
spelling pubmed-31704232011-09-26 Nitric Oxide (NO) and Cyclooxygenase-2 (COX-2) Cross-Talk in Co-Cultures of Tumor Spheroids with Normal Cells Paduch, Roman Kandefer-Szerszeń, Martyna Cancer Microenviron Original Paper Cyclooxygenases (COX), prostaglandin E(2) (PGE(2)) and nitric oxide (NO) are believed to be some of the most important factors related to colon cancer growth and metastasis. In this study, we aimed to investigate the associations between COX-2, PGE(2) and NO in co-cultures of human colon cancer spheroids obtained from different tumor grades with normal human colonic epithelium and myofibroblast monolayers. L-arginine (2 mM), a substrate for nitric oxide synthases (NOS), decreased COX-2 and PGE(2) levels, while N(G)-nitro-L-arginine methyl ester (L-NAME) (2 mM), a NOS inhibitor, had no influence on COX-2 and PGE(2) levels but limited tumor cell motility. NS398 (75 μM), a selective COX-2 inhibitor, had no significant influence on NO level but decreased motility of tumor cells. COX-2, PGE(2) and NO levels depended on the tumor grade of the cells, being the highest in Duke’s stage III colon carcinoma. Summing up, we showed that addition of L-arginine at doses which did not stimulate NO level caused a significant decrease in COX-2 and PGE(2) amounts in co-cultures of colon tumor spheroids with normal epithelial cells and myofibroblasts. Any imbalances in NO level caused by exogenous factors influence COX-2 and PGE(2) amounts depending on the kind of cells, their reciprocal interactions and the local microenvironmental conditions. The knowledge of these effects may be useful in limiting colon carcinoma progression and invasion. Springer Netherlands 2011-02-22 /pmc/articles/PMC3170423/ /pubmed/21909878 http://dx.doi.org/10.1007/s12307-011-0063-x Text en © The Author(s) 2011 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Original Paper
Paduch, Roman
Kandefer-Szerszeń, Martyna
Nitric Oxide (NO) and Cyclooxygenase-2 (COX-2) Cross-Talk in Co-Cultures of Tumor Spheroids with Normal Cells
title Nitric Oxide (NO) and Cyclooxygenase-2 (COX-2) Cross-Talk in Co-Cultures of Tumor Spheroids with Normal Cells
title_full Nitric Oxide (NO) and Cyclooxygenase-2 (COX-2) Cross-Talk in Co-Cultures of Tumor Spheroids with Normal Cells
title_fullStr Nitric Oxide (NO) and Cyclooxygenase-2 (COX-2) Cross-Talk in Co-Cultures of Tumor Spheroids with Normal Cells
title_full_unstemmed Nitric Oxide (NO) and Cyclooxygenase-2 (COX-2) Cross-Talk in Co-Cultures of Tumor Spheroids with Normal Cells
title_short Nitric Oxide (NO) and Cyclooxygenase-2 (COX-2) Cross-Talk in Co-Cultures of Tumor Spheroids with Normal Cells
title_sort nitric oxide (no) and cyclooxygenase-2 (cox-2) cross-talk in co-cultures of tumor spheroids with normal cells
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170423/
https://www.ncbi.nlm.nih.gov/pubmed/21909878
http://dx.doi.org/10.1007/s12307-011-0063-x
work_keys_str_mv AT paduchroman nitricoxidenoandcyclooxygenase2cox2crosstalkincoculturesoftumorspheroidswithnormalcells
AT kandeferszerszenmartyna nitricoxidenoandcyclooxygenase2cox2crosstalkincoculturesoftumorspheroidswithnormalcells