Effects of Angiotensin Ⅱ Receptor 1 Inhibitor on the Proliferation and Apoptosis of Estrogen Induced Human Endometrial Carcinoma Cells / 中国医科大学学报

ABSTRACT

Objective To explore the effects of estrogen and angiotensin Ⅱ receptor 1 inhibitor（saralasin）on cell proliferation,cell cycle and apoptosis in endometrial carcinoma cell line HEC-1A.Methods Immunocytochemical assay was applied to detect the expression of AT1-R,PI3K,p-Akt and ERK protein in HEC-1A cell.The effects of estrogen and saralasin on cell proliferation,cell cycle distribution and apoptosis of HEC-1A cell were detected by MTT assay and fluorescence activated cell sorting technique.The expression of ERK and p-Akt protein in HEC-1A cell treated with estrogen and saralasin were analyzed by Western blot.Results The expression of AT1-R,PI3K,pAkt,and ERK protein was found in HEC-1A cell.Estrogen stimulated the proliferation of HEC-1A cell,decreased G0~G1 phase proportion and increased S phase proportion significantly,minimized the number of apoptotic cells,and up-regulated the expression of ERK protein.Saralasin obviously inhibited the proliferation and induced apoptosis of estrogen induced HEC-1A cell,increased G0~G1 phase proportion and decreased S phase proportion,and down-regulated the expression of ERK protein.Conclusion Estrogen could promote the proliferation of HEC-1A cell through AT1-R.AT1-R inhibitor saralasin could inhibit the proliferation and induce the apoptosis of estrogen induced HEC-1A cell.The down-regulation of ERK protein expression by interrupting the mitogen-activated protein kinase（MAPK）signaling pathway might be involved in the possible mechanism.Thus saralasin could be a valid approach to treat ER-negative endometrial carcinoma.