Cargando…

Deciphering the anti-angiogenic effect of endostatin/cyclophosphamide to normalize tumor micrangium through notch signaling pathway in colon cancer

BACKGROUND: The invasion of colon cancer is associated with the tumor angiogenesis. Endostatin is an important anti-angiogenic agent, and the additive effect of endostatin with a chemotherapeutic agent, cyclophosphamide, on micrangium has not been established. METHODS: Male BALB/c strain nude mice w...

Descripción completa

Detalles Bibliográficos
Autores principales: Lv, Jin-Yan, Hu, Tai-Yuan, Wang, Ruo-Yu, Zhu, Jin-Ming, Wang, Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712526/
https://www.ncbi.nlm.nih.gov/pubmed/26762567
http://dx.doi.org/10.1186/s12957-015-0761-9
_version_ 1782410081311129600
author Lv, Jin-Yan
Hu, Tai-Yuan
Wang, Ruo-Yu
Zhu, Jin-Ming
Wang, Gang
author_facet Lv, Jin-Yan
Hu, Tai-Yuan
Wang, Ruo-Yu
Zhu, Jin-Ming
Wang, Gang
author_sort Lv, Jin-Yan
collection PubMed
description BACKGROUND: The invasion of colon cancer is associated with the tumor angiogenesis. Endostatin is an important anti-angiogenic agent, and the additive effect of endostatin with a chemotherapeutic agent, cyclophosphamide, on micrangium has not been established. METHODS: Male BALB/c strain nude mice were injected with human colorectal carcinoma cells (HCT-116). The mice were divided into four groups (n = 15, each group) and were treated with different concentrations of endostatin (15, 10, and 5 mg/kg/day), cyclophosphamide (20, 10, and 5 mg/kg/day), and combination of endostatin/cyclophosphamide (15 + 20, 15 + 10, and 15 + 5 mg/kg/day). The tumor inhibition rate was evaluated, followed by the quantification of messenger ribonucleic acid (mRNA) and protein expression of notch signaling components NOTCH-1, NOTCH-3, NOTCH-4, JAG-1, DLL-4, Hes-1, and Hey-1 using quantitative polymerase chain reaction (qPCR). The protein expression of NOTCH-3, JAG-1, and DLL-4 was confirmed using western blotting. Microvessel density (MVD) was evaluated to detect micrangium following the treatment. RESULTS: The endostatin/cyclophosphamide-treated samples exhibited an additive effect on the tumor inhibition rate and the microvessel count. NOTCH-1, NOTCH-3, NOTCH-4, JAG-1, Hes-1, and Hey-1 expression levels were highly correlated and downregulated in the treated samples, whereas DLL-4 expression was upregulated that accounted for its anti-angiogenic property. CONCLUSIONS: The combination treatment of colon cancer with endostatin and a chemotherapeutic agent, cyclophosphamide proves to be an efficient therapeutic strategy to inhibit the rapid vasculature formation confirmed by the differential expression of notch signaling components.
format Online
Article
Text
id pubmed-4712526
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-47125262016-01-15 Deciphering the anti-angiogenic effect of endostatin/cyclophosphamide to normalize tumor micrangium through notch signaling pathway in colon cancer Lv, Jin-Yan Hu, Tai-Yuan Wang, Ruo-Yu Zhu, Jin-Ming Wang, Gang World J Surg Oncol Research BACKGROUND: The invasion of colon cancer is associated with the tumor angiogenesis. Endostatin is an important anti-angiogenic agent, and the additive effect of endostatin with a chemotherapeutic agent, cyclophosphamide, on micrangium has not been established. METHODS: Male BALB/c strain nude mice were injected with human colorectal carcinoma cells (HCT-116). The mice were divided into four groups (n = 15, each group) and were treated with different concentrations of endostatin (15, 10, and 5 mg/kg/day), cyclophosphamide (20, 10, and 5 mg/kg/day), and combination of endostatin/cyclophosphamide (15 + 20, 15 + 10, and 15 + 5 mg/kg/day). The tumor inhibition rate was evaluated, followed by the quantification of messenger ribonucleic acid (mRNA) and protein expression of notch signaling components NOTCH-1, NOTCH-3, NOTCH-4, JAG-1, DLL-4, Hes-1, and Hey-1 using quantitative polymerase chain reaction (qPCR). The protein expression of NOTCH-3, JAG-1, and DLL-4 was confirmed using western blotting. Microvessel density (MVD) was evaluated to detect micrangium following the treatment. RESULTS: The endostatin/cyclophosphamide-treated samples exhibited an additive effect on the tumor inhibition rate and the microvessel count. NOTCH-1, NOTCH-3, NOTCH-4, JAG-1, Hes-1, and Hey-1 expression levels were highly correlated and downregulated in the treated samples, whereas DLL-4 expression was upregulated that accounted for its anti-angiogenic property. CONCLUSIONS: The combination treatment of colon cancer with endostatin and a chemotherapeutic agent, cyclophosphamide proves to be an efficient therapeutic strategy to inhibit the rapid vasculature formation confirmed by the differential expression of notch signaling components. BioMed Central 2016-01-14 /pmc/articles/PMC4712526/ /pubmed/26762567 http://dx.doi.org/10.1186/s12957-015-0761-9 Text en © Lv et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Lv, Jin-Yan
Hu, Tai-Yuan
Wang, Ruo-Yu
Zhu, Jin-Ming
Wang, Gang
Deciphering the anti-angiogenic effect of endostatin/cyclophosphamide to normalize tumor micrangium through notch signaling pathway in colon cancer
title Deciphering the anti-angiogenic effect of endostatin/cyclophosphamide to normalize tumor micrangium through notch signaling pathway in colon cancer
title_full Deciphering the anti-angiogenic effect of endostatin/cyclophosphamide to normalize tumor micrangium through notch signaling pathway in colon cancer
title_fullStr Deciphering the anti-angiogenic effect of endostatin/cyclophosphamide to normalize tumor micrangium through notch signaling pathway in colon cancer
title_full_unstemmed Deciphering the anti-angiogenic effect of endostatin/cyclophosphamide to normalize tumor micrangium through notch signaling pathway in colon cancer
title_short Deciphering the anti-angiogenic effect of endostatin/cyclophosphamide to normalize tumor micrangium through notch signaling pathway in colon cancer
title_sort deciphering the anti-angiogenic effect of endostatin/cyclophosphamide to normalize tumor micrangium through notch signaling pathway in colon cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712526/
https://www.ncbi.nlm.nih.gov/pubmed/26762567
http://dx.doi.org/10.1186/s12957-015-0761-9
work_keys_str_mv AT lvjinyan decipheringtheantiangiogeniceffectofendostatincyclophosphamidetonormalizetumormicrangiumthroughnotchsignalingpathwayincoloncancer
AT hutaiyuan decipheringtheantiangiogeniceffectofendostatincyclophosphamidetonormalizetumormicrangiumthroughnotchsignalingpathwayincoloncancer
AT wangruoyu decipheringtheantiangiogeniceffectofendostatincyclophosphamidetonormalizetumormicrangiumthroughnotchsignalingpathwayincoloncancer
AT zhujinming decipheringtheantiangiogeniceffectofendostatincyclophosphamidetonormalizetumormicrangiumthroughnotchsignalingpathwayincoloncancer
AT wanggang decipheringtheantiangiogeniceffectofendostatincyclophosphamidetonormalizetumormicrangiumthroughnotchsignalingpathwayincoloncancer