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Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors

Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) regulate colon cancer growth and metastasis. Previous studies utilizing antibodies against the VEGF receptor (DC101) or EGF receptor (C225) have demonstrated independently that these agents can inhibit tumour growth and indu...

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Autores principales: Shaheen, R M, Ahmad, S A, Liu, W, Reinmuth, N, Jung, Y D, Tseng, W W, Drazan, K E, Bucana, C D, Hicklin, D J, Ellis, L M
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364099/
https://www.ncbi.nlm.nih.gov/pubmed/11506500
http://dx.doi.org/10.1054/bjoc.2001.1936
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author Shaheen, R M
Ahmad, S A
Liu, W
Reinmuth, N
Jung, Y D
Tseng, W W
Drazan, K E
Bucana, C D
Hicklin, D J
Ellis, L M
author_facet Shaheen, R M
Ahmad, S A
Liu, W
Reinmuth, N
Jung, Y D
Tseng, W W
Drazan, K E
Bucana, C D
Hicklin, D J
Ellis, L M
author_sort Shaheen, R M
collection PubMed
description Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) regulate colon cancer growth and metastasis. Previous studies utilizing antibodies against the VEGF receptor (DC101) or EGF receptor (C225) have demonstrated independently that these agents can inhibit tumour growth and induce apoptosis in colon cancer in in vivo and in vitro systems. We hypothesized that simultaneous blockade of the VEGF and EGF receptors would enhance the therapy of colon cancer in a mouse model of peritoneal carcinomatosis. Nude mice were given intraperitoneal injection of KM12L4 human colon cancer cells to generate peritoneal metastases. Mice were then randomized into one of four treatment groups: control, anti-VEGFR (DC101), anti-EGFR (C225), or DC101 and C225. Relative to the control group, treatment with DC101 or with DC101+C225 decreased tumour vascularity, growth, proliferation, formation of ascites and increased apoptosis of both tumour cells and endothelial cells. Although C225 therapy did not change any of the above parameters, C225 combined with DC101 led to a significant decrease in tumour vascularity and increases in tumour cell and endothelial cell apoptosis (vs the DC101 group). These findings suggest that DC101 inhibits angiogenesis, endothelial cell survival, and VEGF-mediated ascites formation in a murine model of colon cancer carcinomatosis. The addition of C225 to DC101 appears to lead to a further decrease in angiogenesis and ascites formation. Combination anti-VEGF and anti-EGFR therapy may represent a novel therapeutic strategy for the management of colon peritoneal carcinomatosis. © 2001 Cancer Research Campaign http://www.bjcancer.com
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spelling pubmed-23640992009-09-10 Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors Shaheen, R M Ahmad, S A Liu, W Reinmuth, N Jung, Y D Tseng, W W Drazan, K E Bucana, C D Hicklin, D J Ellis, L M Br J Cancer Regular Article Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) regulate colon cancer growth and metastasis. Previous studies utilizing antibodies against the VEGF receptor (DC101) or EGF receptor (C225) have demonstrated independently that these agents can inhibit tumour growth and induce apoptosis in colon cancer in in vivo and in vitro systems. We hypothesized that simultaneous blockade of the VEGF and EGF receptors would enhance the therapy of colon cancer in a mouse model of peritoneal carcinomatosis. Nude mice were given intraperitoneal injection of KM12L4 human colon cancer cells to generate peritoneal metastases. Mice were then randomized into one of four treatment groups: control, anti-VEGFR (DC101), anti-EGFR (C225), or DC101 and C225. Relative to the control group, treatment with DC101 or with DC101+C225 decreased tumour vascularity, growth, proliferation, formation of ascites and increased apoptosis of both tumour cells and endothelial cells. Although C225 therapy did not change any of the above parameters, C225 combined with DC101 led to a significant decrease in tumour vascularity and increases in tumour cell and endothelial cell apoptosis (vs the DC101 group). These findings suggest that DC101 inhibits angiogenesis, endothelial cell survival, and VEGF-mediated ascites formation in a murine model of colon cancer carcinomatosis. The addition of C225 to DC101 appears to lead to a further decrease in angiogenesis and ascites formation. Combination anti-VEGF and anti-EGFR therapy may represent a novel therapeutic strategy for the management of colon peritoneal carcinomatosis. © 2001 Cancer Research Campaign http://www.bjcancer.com Nature Publishing Group 2001-08 /pmc/articles/PMC2364099/ /pubmed/11506500 http://dx.doi.org/10.1054/bjoc.2001.1936 Text en Copyright © 2001 Cancer Research Campaign 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 Regular Article
Shaheen, R M
Ahmad, S A
Liu, W
Reinmuth, N
Jung, Y D
Tseng, W W
Drazan, K E
Bucana, C D
Hicklin, D J
Ellis, L M
Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors
title Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors
title_full Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors
title_fullStr Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors
title_full_unstemmed Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors
title_short Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors
title_sort inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364099/
https://www.ncbi.nlm.nih.gov/pubmed/11506500
http://dx.doi.org/10.1054/bjoc.2001.1936
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