Regulation of prostate cancer cell growth and PSA expression by angiotensin II receptor blocker with peroxisome proliferator-activated receptor gamma ligand like action.

摘要

BACKGROUND: We previously reported that angiotensin II (AII) activated the proliferation of prostate cancer cells, and its antagonist, an AII receptor type 1 (AT1R) blocker (ARB), inhibited the proliferation of prostate cancer in vitro and in vivo. In the present study, we investigated whether telmisartan, an ARB, has a unique feature as a peroxisome proliferator-activated receptor gamma (PPARgamma) ligand, and its suppressive potential on prostate cancer cells. METHODS: Cell count or MTT assay were carried out for growth suppression of prostate cancer cells. Phosphorylation of mitogen-activated protein kinase (MAPK), specific expression of prostate specific antigen (PSA) and AT1R were investigated by western blot. To confirm the PPARgamma activity of ARBs, luciferase assay using PSA promoter and PPARgamma response elements (PPRE) plasmids was performed. RESULTS: The results showed that cell proliferation and signal transduction were inhibited by telmisartan treatment. Also, inhibition of PSA expression by telmisartan was confirmed by western blot and luciferase assay, indicating that an ARB acted in a similar way such as an anti-androgenic agent in prostate cancer cells. CONCLUSION: The present study showed ARBs, especially those possessing a PPARgamma ligand-like structure, have a potential antagonistic effect on androgen-dependent and -independent prostate cancer.