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

33Citations
Citations of this article
23Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

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. © 2011 Cancer Research UK All rights reserved.

Cite

CITATION STYLE

APA

Tanaka, N., Miyajima, A., Kosaka, T., Miyazaki, Y., Shirotake, S., Shirakawa, H., … Oya, M. (2011). Acquired platinum resistance enhances tumour angiogenesis through angiotensin II type 1 receptor in bladder cancer. British Journal of Cancer, 105(9), 1331–1337. https://doi.org/10.1038/bjc.2011.399

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free