Acquired platinum resistance enhances tumour angiogenesis through angiotensin II type 1 receptor in bladder cancer
Related Experiment Video
Updated: May 28, 2026
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
N Tanaka1, A Miyajima, T Kosaka
1Department of Urology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
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.
Insights
Acquired platinum resistance in bladder cancer involves increased reactive oxygen species (ROS) and angiotensin II (Ang II) type 1 receptor (AT1R) signaling. Blocking AT1R shows promise for treating platinum-resistant bladder tumors.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Investigated reactive oxygen species (ROS) and angiogenesis via angiotensin II (Ang II) type 1 receptor (AT1R) in acquired platinum-resistant bladder cancer.
- Examined molecular changes following cisplatin (CDDP) treatment in bladder cancer models.
Purpose of the Study:
- To elucidate the role of AT1R and ROS in the development of platinum resistance in bladder cancer.
- To evaluate the therapeutic potential of AT1R blockade in platinum-resistant bladder cancer.
Main Methods:
- Utilized human bladder cancer cell lines (T24, 5637) and their acquired platinum-resistant sublines (T24PR, 5637PR) in vitro and in vivo.
- Assessed vascular endothelial growth factor (VEGF) production, AT1R expression, and ROS levels.
- Investigated the effect of AT1R blockade and free radical scavenging on tumor growth in xenograft models.
Main Results:
- Platinum-resistant cells exhibited significantly higher VEGF production and AT1R expression induced by Ang II compared to parent cells.
- ROS levels were significantly upregulated in resistant cells, and AT1R expression was downregulated by free radical scavenging.
- AT1R blockade effectively suppressed the growth of platinum-resistant bladder cancer xenografts.
Conclusions:
- Upregulated AT1R signaling through increased ROS is a key mechanism in bladder cancer progression after CDDP treatment.
- AT1R blockade represents a potential therapeutic strategy for platinum-resistant bladder cancers.
Related Concept Videos
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
01:10Mechanism of Angiogenesis