Effects of Inhibitors of the Activity of the Circulating Renin-Angiotensin System on the Growth and Proliferation of Endometrial Cancer Cells.

Endometrial cancers increase expression of the renin-angiotensin system (RAS). This study aimed to determine if inhibiting the RAS would reduce the viability and proliferation of endometrial cancer cells. The expression of RAS genes was measured in three endometrial epithelial adenocarcinoma cell lines (Ishikawa, HEC-1-A, AN3CA). Ishikawa cells had the highest expression of REN, ACE, and AGTR1 mRNA. AGT mRNA and protein levels were most abundant in HEC-1-A cells. We then determined the effects of drugs that inhibit the action of renin (VTP-27999 and aliskiren) or angiotensin-converting enzyme (perindoprilat) or block the angiotensin II type 1 receptor (losartan and telmisartan). Overall, VTP-27999, aliskiren, perindoprilat, and losartan had minimal effects on cell viability in all three cell lines, and combinations of these drugs did not have any effect. Telmisartan (a dual angiotensin receptor blocker and PPAR-γ agonist) significantly reduced the viability of all three cell lines and reduced the proliferation of both Ishikawa and AN3CA cells. Telmisartan was more effective than troglitazone (PPAR-γ agonist) in Ishikawa and HEC-1-A cells. RAS inhibitors were most effective in Ishikawa cells, which had the highest levels of RAS expression. Therefore, levels of RAS expression in endometrial cancers might indicate the potential efficacy of RAS drugs.