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苦参碱通过抑制PI3K/Akt/mTOR信号通路诱导急性髓系白血病细胞凋亡。

Matrine induces apoptosis in acute myeloid leukemia cells by inhibiting the PI3K/Akt/mTOR signaling pathway.

作者信息

Hao Yanmei, Zhang Nan, Wei Nannan, Yin Hongmei, Zhang Yingjie, Xu Hui, Zhu Chaomang, Li Duojie

机构信息

Department of Clinical Laboratory, Bengbu Medical College, Bengbu, Anhui 233004, P.R. China.

Department of Radiotherapy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China.

出版信息

Oncol Lett. 2019 Sep;18(3):2891-2896. doi: 10.3892/ol.2019.10649. Epub 2019 Jul 22.

Abstract

Matrine has been demonstrated to exert anticancer effects on acute myeloid leukemia (AML) cell lines. However, the mechanisms of matrine in AML remain largely unknown. The present study investigated the anticancer effects and underlying mechanisms of matrine on human AML cells . THP-1 cell lines were cultured and treated with different doses of matrine (0.4, 0.8, 1.2, 1.6 and 2.0 g/l). The effects of matrine on the cell proliferation were assessed by the Cell Counting Kit-8 assay. The apoptotic effects were evaluated by DAPI and annexin V/propidium iodide staining assays. The effects of the drug on phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ mechanistic target of rapamycin kinase (mTOR) protein expression were studied by western blot analysis. The results of the present study demonstrated that matrine suppressed the viability of THP-1 cells. The anticancer effects were identified to be dose-dependent and the IC value was 1.2 g/l in THP-1 cells. Matrine inhibited cell viability and induced cell apoptosis of AML cell lines in a dose- and time-dependent manner. In addition, it was observed that matrine decreased the expression of phosphorylated (p)-PI3K, p-Akt and p-mTOR in a concentration-dependent manner. However, the expression levels of PI3K, Akt and mTOR remained almost unaltered. These findings indicated that matrine may inhibit cell proliferation and induce apoptosis of AML cells and may be a novel effective chemotherapeutic agent against AML.

摘要

苦参碱已被证明对急性髓系白血病(AML)细胞系具有抗癌作用。然而,苦参碱在AML中的作用机制仍 largely 未知。本研究调查了苦参碱对人AML细胞的抗癌作用及其潜在机制。培养 THP-1 细胞系并用不同剂量的苦参碱(0.4、0.8、1.2、1.6 和 2.0 g/l)进行处理。通过细胞计数试剂盒-8 法评估苦参碱对细胞增殖的影响。通过 DAPI 和膜联蛋白 V/碘化丙啶染色法评估凋亡作用。通过蛋白质印迹分析研究该药物对磷酸肌醇 3-激酶(PI3K)/蛋白激酶 B(Akt)/雷帕霉素激酶机制靶点(mTOR)蛋白表达的影响。本研究结果表明,苦参碱抑制了 THP-1 细胞的活力。抗癌作用呈剂量依赖性,在 THP-1 细胞中的 IC 值为 1.2 g/l。苦参碱以剂量和时间依赖性方式抑制 AML 细胞系的细胞活力并诱导细胞凋亡。此外,观察到苦参碱以浓度依赖性方式降低磷酸化(p)-PI3K、p-Akt 和 p-mTOR 的表达。然而,PI3K、Akt 和 mTOR 的表达水平几乎未改变。这些发现表明,苦参碱可能抑制 AML 细胞的增殖并诱导其凋亡,可能是一种针对 AML 的新型有效化疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a918/6704321/62d1b6eb3f15/ol-18-03-2891-g00.jpg

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