Inhibition of 11βHSD2 activity with GA suppressed tumor growth through activation of glucocorticoid receptors.
(A) GA augmented low-dose CS–induced inhibition of CT26 cell COX-2 expression. (B) Treatment with 10 mg/kg/d GA i.p. led to significant decreases in tumor size, COX-2 expression, and PGE2 levels, which were completely reversed by the glucocorticoid receptor inhibitor RU486 (7.5 mg/kg/d i.m.). n = 5–6 per group. (C) GA reduced CT26 tumor expression of phosphorylated cPLA2 (P-cPLA2) and mPGES-1, but had no effect on tumor expression of COX-1 (P = 0.23) and cPGES (P = 0.055). Original magnification, ×400. (D) GA treatment significantly increased corticosterone levels and decreased 11-keto-corticosterone levels in kidney, colon, and tumors. n = 5. *P < 0.0001, **P < 0.001, ***P < 0.02, #P < 0.05, ##P < 0.01, and ###P < 0.005 versus vehicle.