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阿帕替尼通过下调缺氧诱导因子-1 和增加活性氧水平促进胰腺癌细胞凋亡。

Apatinib Promotes Apoptosis of Pancreatic Cancer Cells through Downregulation of Hypoxia-Inducible Factor-1 and Increased Levels of Reactive Oxygen Species.

机构信息

Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.

Center for Stem Cell Biology and Tissue Engineering, Key Laboratory of Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China.

出版信息

Oxid Med Cell Longev. 2019 Feb 4;2019:5152072. doi: 10.1155/2019/5152072. eCollection 2019.

Abstract

At present, apatinib is considered a new generation agent for the treatment of patients with gastric cancer. However, the effects of apatinib on pancreatic cancer have not been clarified. This study investigated the impact of apatinib on the biological function of pancreatic cancer cells and the potential mechanism involved in this process. Using the Cell Counting Kit-8 method, we confirmed that apatinib treatment inhibited cell proliferation . Moreover, the migration rate of pancreatic cells was inhibited. The effects of apatinib on apoptosis and cell cycle distribution of pancreatic carcinoma cells were detected by flow cytometry. The number of apoptotic cells was significantly increased, and the cell cycle was altered. Furthermore, we demonstrated that apatinib inhibited the expression of hypoxia-inducible factor-1 (HIF-1), vascular endothelial growth factor, and markers of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling pathway, which increased the levels of reactive oxygen species Apatinib significantly inhibited the biological function of pancreatic cancer cells. It promoted apoptosis, downregulated the expression of HIF-1, and increased the levels of reactive oxygen species.

摘要

目前,阿帕替尼被认为是治疗胃癌患者的新一代药物。然而,阿帕替尼对胰腺癌的作用尚未阐明。本研究旨在探讨阿帕替尼对胰腺癌细胞生物学功能的影响及其潜在机制。我们采用细胞计数试剂盒-8 法证实阿帕替尼处理可抑制细胞增殖,而且抑制胰腺细胞的迁移率。通过流式细胞术检测阿帕替尼对胰腺癌细胞凋亡和细胞周期分布的影响。结果显示,阿帕替尼作用后凋亡细胞数量明显增加,细胞周期发生改变。此外,我们证明阿帕替尼可抑制缺氧诱导因子-1(HIF-1)、血管内皮生长因子以及磷酸肌醇 3-激酶(PI3K)/Akt/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路标志物的表达,增加活性氧水平。阿帕替尼可显著抑制胰腺癌细胞的生物学功能,促进细胞凋亡,下调 HIF-1 的表达,增加活性氧水平。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2041/6378789/a417559c9385/OMCL2019-5152072.001.jpg

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