Abstract: Objective To investigatethe potential effects of simvastatin on angiotensin II-stimulatedsecretion and proliferation of adrenocortical carcinoma H295R cells. Methods The H295R cells were divided into control group, Angiotensin II group, simvastatin group and Angiotensin II plus simvastatin group. Cortisol in medium was determined by chemiluminescent method, and aldosterone was determined by radioimmunoassay. The mRNA expressions of 11 beta-hydroxylase(CYP11B1) and aldosterone synthase(CYP11B2) were examined by real-time quantitative PCR. Cell proliferation was detected by MTS method. Results Compared with control group, angiotensin II increased the secretion of cortisol and aldosterone, and the expression of CYP11B1 and CYP11B2. Simvastatin decreased cortisol secretion and CYP11B1 mRNA expression (P < 0.05). Simvastatin also inhibited angiotensin II-induced the secretion of cortisol and aldosterone, and the expression of CYP11B1 and CYP11B2 compared with Angiotensin II group(P < 0.05). Angiotensin II had no effects on the cell proliferation, while simvastatin significantlyinhibited cell proliferation. The inhibitory effect of simvastatin on proliferation was enhanced when simvastatin combined with angiotensin II(P < 0.05). Conclusions Simvastatin can inhibit angiotensin II-induced secretion of cortisol and aldosterone in H295R cells. Simvastatin inhibits cell proliferation, which could be enhanced by simvastatin combined with angiotensin II.

Key words: simvastatin, angiotensin II, H295R cell, secretion function, cell proliferation