Salvianolic acid A, a novel PI3K/Akt inhibitor, induces cell apoptosis and suppresses tumor growth in acute myeloid leukemia
Salvianolic acid A, a novel PI3K/Akt inhibitor, induces cell apoptosis and suppresses tumor growth in acute myeloid leukemia
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丹酚酸 A 是一种新型 PI3K/Akt 抑制剂，在急性髓性白血病中诱导细胞凋亡并抑制肿瘤生长
DOI：
10.1080/10428194.2017.1399314
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发表时间：
2018-01-01
影响因子：
2.6
通讯作者：
Jiang, Lei
中科院分区：
文献类型：
--
作者：
Pei, Renzhi;Si, Ting;Jiang, Lei
丹参素A（Salvioleacid A，SAA）是丹参的主要衍生物之一，具有抗炎和抗血栓形成的作用。然而，它在抑制肿瘤生长中的作用仍然难以捉摸。本研究旨在探讨SAA对急性髓细胞白血病（AML）的治疗作用。在此，SAA在AML细胞中显示出剂量依赖性的细胞活力抑制和细胞凋亡诱导。在分子水平上，SAA通过PARP裂解和caspase-3激活，增加了巴克的表达，降低了Bcl-xL的表达。SAA还显著减弱AML细胞中Akt磷酸化。在异种移植小鼠模型中，SAA在体内显著抑制AML肿瘤的生长。此外，SAA对原发性AML细胞比对良性疾病患者的骨髓单个核细胞表现出更深刻的促凋亡作用。因此，SAA的促凋亡和抗肿瘤特性表明其对AML具有潜在的治疗价值。
Salvianolic acid A (SAA), one of the main derivatives of Salvia miltiorrhiza, has been shown to possess anti-inflammatory and anti-thrombotic activities. Its role in inhibiting tumor growth, however, remains elusive. The aim of this study was to investigate the effect of SAA on acute myeloid leukemia (AML). Here, SAA showed a dose-dependent cell viability inhibition and apoptosis induction in AML cells. At the molecular level, SAA increased the expression of Bak and decreased the expression of Bcl-xL, following by PARP cleavage and caspase-3 activation. SAA also markedly attenuated Akt phosphorylation in AML cells. In a xenograft mouse model, SAA significantly suppressed the growth of AML tumors in vivo. Furthermore, SAA exhibited a more profound pro-apoptotic effect on primary AML cells than on bone marrow mononuclear cells from patients with benign diseases. Therefore, the pro-apoptotic and anti-tumor properties of SAA suggested its promising therapeutic value for AML.