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Acquired platinum resistance enhances tumour angiogenesis through angiotensin II type 1 receptor in bladder cancer

BACKGROUND: We investigated the changes in reactive oxygen species (ROS) and angiogenesis through angiotensin II (Ang II) type 1 receptor (AT1R) after the development of acquired platinum resistance in bladder cancer. METHODS: Four invasive human bladder cancer cell lines, T24, 5637, T24PR, and 5637...

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Autores principales: Tanaka, N, Miyajima, A, Kosaka, T, Miyazaki, Y, Shirotake, S, Shirakawa, H, Kikuchi, E, Oya, M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241561/
https://www.ncbi.nlm.nih.gov/pubmed/21970881
http://dx.doi.org/10.1038/bjc.2011.399
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author Tanaka, N
Miyajima, A
Kosaka, T
Miyazaki, Y
Shirotake, S
Shirakawa, H
Kikuchi, E
Oya, M
author_facet Tanaka, N
Miyajima, A
Kosaka, T
Miyazaki, Y
Shirotake, S
Shirakawa, H
Kikuchi, E
Oya, M
author_sort Tanaka, N
collection PubMed
description BACKGROUND: We investigated the changes in reactive oxygen species (ROS) and angiogenesis through angiotensin II (Ang II) type 1 receptor (AT1R) after the development of acquired platinum resistance in bladder cancer. METHODS: Four invasive human bladder cancer cell lines, T24, 5637, T24PR, and 5637PR, were used in vitro, whereas in vivo, T24 and T24PR cells were used. T24PR and 5637PR cells were newly established at our institution as acquired platinum-resistant sublines by culturing in cisplatin (CDDP)-containing conditioned medium for 6 months. RESULTS: Ang II induced significantly higher vascular endothelial growth factor (VEGF) production in T24PR and 5637PR cells than in their corresponding parent cells in vitro, whereas Ang II induced a further increase in VEGF production. These platinum-resistant cells also showed significantly higher AT1R expression than their corresponding parent cells. ROS was also significantly upregulated in T24PR and 5637PR cells, whereas increased AT1R expression was significantly downregulated by scavenging free radicals. We also demonstrated the efficacy of AT1R blockade at suppressing the growth of platinum-resistant xenograft model. CONCLUSION: Our findings indicate a new molecular mechanism for upregulated AT1R signalling through increased ROS when tumours progressed after the CDDP-based regimens, and shed light on the importance of AT1R blockade for platinum-resistant bladder cancers.
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spelling pubmed-32415612012-10-25 Acquired platinum resistance enhances tumour angiogenesis through angiotensin II type 1 receptor in bladder cancer Tanaka, N Miyajima, A Kosaka, T Miyazaki, Y Shirotake, S Shirakawa, H Kikuchi, E Oya, M Br J Cancer Translational Therapeutics BACKGROUND: We investigated the changes in reactive oxygen species (ROS) and angiogenesis through angiotensin II (Ang II) type 1 receptor (AT1R) after the development of acquired platinum resistance in bladder cancer. METHODS: Four invasive human bladder cancer cell lines, T24, 5637, T24PR, and 5637PR, were used in vitro, whereas in vivo, T24 and T24PR cells were used. T24PR and 5637PR cells were newly established at our institution as acquired platinum-resistant sublines by culturing in cisplatin (CDDP)-containing conditioned medium for 6 months. RESULTS: Ang II induced significantly higher vascular endothelial growth factor (VEGF) production in T24PR and 5637PR cells than in their corresponding parent cells in vitro, whereas Ang II induced a further increase in VEGF production. These platinum-resistant cells also showed significantly higher AT1R expression than their corresponding parent cells. ROS was also significantly upregulated in T24PR and 5637PR cells, whereas increased AT1R expression was significantly downregulated by scavenging free radicals. We also demonstrated the efficacy of AT1R blockade at suppressing the growth of platinum-resistant xenograft model. CONCLUSION: Our findings indicate a new molecular mechanism for upregulated AT1R signalling through increased ROS when tumours progressed after the CDDP-based regimens, and shed light on the importance of AT1R blockade for platinum-resistant bladder cancers. Nature Publishing Group 2011-10-25 2011-10-04 /pmc/articles/PMC3241561/ /pubmed/21970881 http://dx.doi.org/10.1038/bjc.2011.399 Text en Copyright © 2011 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 Translational Therapeutics
Tanaka, N
Miyajima, A
Kosaka, T
Miyazaki, Y
Shirotake, S
Shirakawa, H
Kikuchi, E
Oya, M
Acquired platinum resistance enhances tumour angiogenesis through angiotensin II type 1 receptor in bladder cancer
title Acquired platinum resistance enhances tumour angiogenesis through angiotensin II type 1 receptor in bladder cancer
title_full Acquired platinum resistance enhances tumour angiogenesis through angiotensin II type 1 receptor in bladder cancer
title_fullStr Acquired platinum resistance enhances tumour angiogenesis through angiotensin II type 1 receptor in bladder cancer
title_full_unstemmed Acquired platinum resistance enhances tumour angiogenesis through angiotensin II type 1 receptor in bladder cancer
title_short Acquired platinum resistance enhances tumour angiogenesis through angiotensin II type 1 receptor in bladder cancer
title_sort acquired platinum resistance enhances tumour angiogenesis through angiotensin ii type 1 receptor in bladder cancer
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241561/
https://www.ncbi.nlm.nih.gov/pubmed/21970881
http://dx.doi.org/10.1038/bjc.2011.399
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