【摘要】 目的:观察血管紧张素Ⅱ1型受体(AT1R)拮抗剂坎地沙坦抑制血管紧张素Ⅱ(AngⅡ)介导的原代急性髓样白血病(AML)细胞增殖的作用及机制。方法:MTT法观察AngⅡ对原代AML细胞、正常骨髓单个核细胞增殖的影响以及坎地沙坦和AT2R拮抗剂PD123319对AngII促原代AML细胞增殖的拮抗作用;Western blot-ting法观察坎地沙坦和PI3K抑制剂对原代AML细胞Akt磷酸化的影响。结果:AngII能剂量和时间依赖性促进原代AML细胞增殖(P<0.05),而对正常骨髓无此作用。坎地沙坦随浓度和时间依赖性阻断Ang II作用下白血病细胞增殖(P<0.05)。PI3K抑制剂可抑制Ang II促进原代AML细胞的增殖(P<0.05),坎地沙坦能明显下调Ang II增加原代AML细胞Akt的磷酸化水平(P<0.05)。结论:坎地沙坦通过抑制PI3K/Akt信号转导途径抑制Ang II/AT1R介导的白血病细胞增殖。更多还原

【Abstract】 AIM: To explore the antagonistic effect and mechanism of candesartan on angiotensin II(Ang II)-induced proliferation of primary acute myeloid leukemia(AML)cells. METHODS: MTT assay was used to observe the proliferation effect of Ang II on primary AML cells and normal bone marrow mononuclear cells,and the antagonistic effects of candesartan[an antagonist of angiotensin Ⅱ type 1 receptor(AT1R)] and PD123319(an antagonist of AT2R) were also observed.Akt phosphorylation was detected by Western blotting when the cells were treated with candesartan and a PI3K inhibitor LY294002. RESULTS: Compared with the control cells,Ang II significantly increased the proliferation of AML cells in a dose-and time-dependent manner(P<0.05).Ang II did not stimulate the proliferation of normal bone marrow mononuclear cells.The proliferative effect of Ang II was effectively blocked by the AT1R blocker candesartan(P<0.05).PI3K inhibitor strongly repressed the Ang II-induced cell proliferation(P<0.05).Candesartan significantly reduced Akt phosphorylation promoted by Ang II on primary AML cells(P<0.05). CONCLUSION: Candesartan effectively inhibits Ang II-induced proliferation of primary AML cells by down-regulating PI3K/Akt signaling pathway,indicating a new possible treatment mechanism in some AML cells.更多还原