期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 47, 期 3, 页码 981-993出版社
KARGER
DOI: 10.1159/000490142
关键词
Shikonin; Chronic myeloid leukemia; Proliferation; Apoptosis; PTEN
资金
- Education Foundation of Zhejiang province [Y201636954]
- Zhejiang Provincial Natural Science Foundation [Q17H090034, LY15C090006]
- Science and Technology Planning Project of Zhejiang Province [2017C33197]
- Medical and Health Science and Technology Project of Zhejiang Province [2017209265, 2018277310]
- Zhejiang Medical College Youth Dr. start-up funding [2015B07]
- Outstanding Youth Foundation of Zhejiang Provincial People's Hospital [ZRY2016B007, ZRY2016A003]
Background/Aims: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. Tyrosine kinase inhibitors (TKIs) are commonly used to treat CML; however, drug resistance of CML cells to TKIs has limited their clinical application. Shikonin, a traditional Chinese herb, has long been used to treat leukemia in China, but the roles and related molecular mechanisms of shikonin treatment in CML remain unclear. Here, we aimed to evaluate the effects of shikonin on the proliferation, apoptosis, and migration of K562 cells, a CML cell line. Methods: Firstly, K562 cell proliferation and apoptosis were tested by CCK8 assay and flow cytometry with Annexin V-FITC/PI staining. Cell migration was measured by Transwell migration assay. In addition, western blot was performed to determine the proteins (PI3K, Bax, Bcl-2, cleaved caspase-3, PTEN, p-AKT, AKT, CXCR4, SDF-1, CD44) involved in the mechanism of action of shikonin. Finally, neutrophils from peripheral blood of CML patients were obtained, and cell proliferation and apoptosis were tested by CCK8 assay and flow cytometry. Results: Shikonin reduced the proliferation of K562 cells in a time-and dose-dependent manner and promoted the apoptosis of K562 cells. Moreover, shikonin increased the PTEN level and inactivated the PI3K/AKT signaling pathway, subsequently upregulating BAX in K562 cells. In addition, shikonin could block K562 cell migration via the CXCR4/SDF-1 axis. Finally, shikonin significantly inhibited the proliferation and promoted the apoptosis of neutrophils from CML patients. Conclusion: These results demonstrated that shikonin inhibits CML proliferation and migration and induces apoptosis by the PTEN/PI3K/AKT pathway, revealing the effects of shikonin therapy on CML. (C) 2018 The Author(s) Published by S. Karger AG, Basel
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据