Angiotensin receptor signaling and prostate tumor growth in mice
Jem Scott-Emuakpor, Emma Allott, Stacy A. Johnson, Lauren E. Howard, Everardo Macias, Stephen J. Freedland and Susan B. Gurley
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.
Keywords: AT1R, AT2R, mouse, RAS, angiotensin, tumor, cancer, prostate
Abbreviations: Prostate cancer (PC); Renin-Angiotensin System (RAS); Type 1 Angiotensin Receptor (AT1R); Type 2 Angiotensin Receptor (AT2R)