坎地沙坦阻断血管紧张素Ⅱ介导的原代急性髓样白血病细胞增殖的作用及机制

目的: 观察血管紧张素Ⅱ 1型受体(AT1R)拮抗剂坎地沙坦抑制血管紧张素Ⅱ(Ang Ⅱ)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Ang Ⅱ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 blotting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。

Antagonistic effect of angiotensin II type 1 receptor blocker candesartan on angiotensin II-induced proliferation of primary acute myeloid leukemia cells

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 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.