Na+/Ca2+交换体抑制剂SN-6和维拉帕米降低肾上腺皮质癌细胞系NCI-H295R醛固酮合成酶表达OACSTPCD

Objective To investigate the effect of Na+/Ca2+exchanger inhibitors SN-6 and calcium channel blocker verapamil on potassium-stimulated expression of aldosterone synthase in adrenocortical carcinoma cell line NCI-H295R(H295R).Methods H295R cells were treated in different groups,including control group,K+(15 mmol/L)treated group,verapamil(10 μmol/L)group,SN-6(10 μmol/L)group,combination of K+/verapamil treated group,combination of K+/SN-6 treated group,combination of K+/verapamil and SN-6 treated group.Real-time PCR was used to detect the mRNA expression of aldosterone synthetase(CYP11B2),and FLIPR Calcium 6 was used to detect the intracellular calcium ion level.Results Compared with the control group,K+stimulated CYP11B2 mRNA expression.Both SN-6 and verapamil decreased K+induced CYP11B2 mRNA expression(P＜0.01).Compared with the K++SN-6 treated group,the K+,SN-6 and verapamil treated group all significantly inhibited CYP11B2 mRNA expression(P＜0.001).Both of SN-6 and verapamil significantly reduced the intracel-lular calcium level stimulated by K+(P＜0.0001).Conclusions Both SN-6 and verapamil inhibit K+-induced ex-pression of aldosterone synthase in adrenocortical carcinoma H295R cells.The inhibitory effect is more significant when treated by the combination of verapamil and SN6.