心钠素对多发性骨髓瘤细胞增殖及微小RNA-21表达的影响

Effects of Atrial Natriuretic Peptide on the Proliferation of Myeloma Cells and microRNA-21 Expression

目的探讨心钠素（ANP）对多发性骨髓瘤（MM）细胞增殖的影响及其抗癌机制。方法以MM1.S细胞为研究对象,观察不同浓度ANP对MM细胞增殖与周期的影响,检测A型利钠肽受体（NPR-A）与C型利钠肽受体（NPR-C）蛋白表达,并分析ANP对MM细胞miRNA-21表达的影响。结果 1～100μmol/L ANP以浓度依赖性抑制MM细胞增殖;其中,在24h时间点ANP对MM1.S细胞增殖抑制作用最强;随着时间延长,ANP抑制作用呈减弱趋势。ANP作用MM1.S细胞24h后,与对照组比较,各组G1期细胞比例均增加,S期与G2期细胞比例下降,PI及miRNA-21表达均低于对照组（P〈0.01,P〈0.05）。MM1.S细胞上存在NPR-A与NPR-C受体。结论 ANP与NPR-A/C受体结合,通过阻滞细胞周期于G1期与抑制miR-21表达,发挥抗MM细胞增殖作用。

Objective To explore the effects of Atrial Natriuretic Peptide（ ANP） on cell proliferation of multiple myeloma（ MM） and its anticancer mechanisms. Methods The MM1. S cells were used in this study,and the effects of different concentrations of ANP on cell proliferation and cell cycle were observed. The protein expressions of natriuretic peptide receptor-A（ NPR-A） and NPR-C were detected,and the effect of ANP on microRNA-21（ miR-21） expression in MM1. S cells were also analyzed. Results The 1-100 μmol / L ANP inhibited the MM cell proliferation in a dose-dependent manner; at the 24 thh,ANP had the most potent anti-proliferative activity against MM cells,and then anti-proliferative activity became weaker and weaker with time went by. After ANP affected MM1. S cells for 24 h,compared with those in control group,the cell ratios in G1 phase were increased,while the cell ratios in S and G2 phases were decreased,and the expressions of proliferation index（ PI） and miRNA were lower than those in control group（ P〈0. 01,P 0. 05）.The NPR-A and NPR-C receptors were found in MM1. S cells. Conclusion ANP in combination of NPR-A / C receptor has anti-proliferative effect in MM cells by blocking cell cycle in G1 phase and inhibiting the miR-21 expression.