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Updated: Feb 21, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Angiotensin receptor signaling and prostate tumor growth in mice
Jem Scott-Emuakpor1,2, Emma Allot3,4,5, Stacy A Johnson1,6,7,8
1Department of Research and Development, Durham VA Medical Center, USA.
Objective:
The renin-angiotensin system, through its type 1 and type 2 angiotensin receptors (AT1R and AT2R, respectively) may have a role in prostate cancer. The objective of this pilot study was to explore that potential role by determining whether the AT1R blocker, losartan, would reduce the growth of LAPC-4 prostate cancer xenografts in nude mice. We also evaluated the tumor growth effects of using angiotensin II to activate both AT1R and AT2R simultaneously. Our data showed that losartan decreased tumor volumes by 56% versus control. This decrease reached statistical significance at day 54 (p = 0.0014). By day 54, Ki67 was also reduced in the losartan group, though not significantly so (p = 0.077). Losartan had no significant effect on AT1R or AT2R expression. Despite significant increases in both AT1R and AT2R at day 29 (p = 0.043 and 0.038, respectively), the administration of angiotensin II did not result in any significant differences in tumor volumes or ki67 at any time point. These data suggest that selective activation and induction of AT2R coupled with blockade of AT1R may slow prostate cancer growth. Future larger studies are needed to confirm these results.
Insights
Losartan, an AT1R blocker, significantly reduced prostate cancer xenograft growth in mice by 56%. This suggests blocking the angiotensin II type 1 receptor (AT1R) may slow prostate cancer progression.
Area of Science:
- Oncology
- Endocrinology
- Pharmacology
Background:
- The renin-angiotensin system (RAS) and its receptors, angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R), are implicated in prostate cancer.
- Understanding the role of AT1R and AT2R in prostate cancer progression is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the potential role of the RAS in prostate cancer.
- To determine if losartan, an AT1R blocker, inhibits the growth of LAPC-4 prostate cancer xenografts in nude mice.
- To evaluate the effect of simultaneous AT1R and AT2R activation by angiotensin II on tumor growth.
Main Methods:
- Pilot study using LAPC-4 prostate cancer xenografts in nude mice.
- Treatment with losartan (AT1R blocker) or angiotensin II (to activate AT1R and AT2R).
- Tumor volume and Ki67 proliferation index were measured over time.
Main Results:
- Losartan significantly decreased tumor volumes by 56% compared to controls (p = 0.0014 at day 54).
- Ki67 was reduced in the losartan group, but not significantly (p = 0.077).
- Angiotensin II administration did not significantly alter tumor volumes or Ki67 levels.
Conclusions:
- Blocking the AT1R with losartan shows potential in slowing prostate cancer xenograft growth.
- Selective AT2R activation combined with AT1R blockade may inhibit prostate cancer progression.
- Further large-scale studies are warranted to validate these findings.
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