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毛蕊异黄酮通过诱导 caspase 依赖性内在途径、ROS 产生、细胞迁移和侵袭抑制以及靶向 JAK/STAT 信号通路,抑制人肺癌细胞的增殖。

Astragalin flavonoid inhibits proliferation in human lung carcinoma cells mediated via induction of caspase-dependent intrinsic pathway, ROS production, cell migration and invasion inhibition and targeting JAK/STAT signalling pathway.

机构信息

Department of Respiratory and Critical Care Medicine, Wuhan Central Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei Province, 430014, China .

出版信息

Cell Mol Biol (Noisy-le-grand). 2021 Sep 29;67(2):44-49. doi: 10.14715/cmb/2021.67.2.7.

Abstract

The aim of the current study was to investigate the anti-lung cancer effects of astragalin. Studies were also undertaken to evaluate its effects on apoptosis induction, ROS production, cellular migration and invasion and JAK/STAT3 signalling pathway. MTT assay was used to evaluate cell viability in NSCLC A549 cells after exposure to astragalin molecule. Apoptosis was investigated using AO/EB staining, comet assay and western blotting assay. Fluorescence microscopy was implemented to estimate ROS production. Cell migration and invasion were measured using transwell chambers assay. Effects of astragalin on JAK/STAT pathway were investigated using western blotting assay. Results showed astragalin molecule induced inhibition of proliferation in A549 cells in a dose-dependent fashion. Further, the antiproliferative effects were found to mediate via apoptosis as suggested by AO/EB staining and western blotting assay. Astragalin modulated the expressions of caspase-3, caspase-9, Bax, Bak, Cyt-c Bcl-2, XIAP and Bcl-xL. Astragalin induced DNA damage in A549 cells which too indicated apoptotic cell death. Astragalin molecule enhanced the production of ROS by A549 cells. It inhibited both cell migration and invasion of A549 cells in a concentration-dependent manner. Finally, astragalin drug was observed with remarkable potential of targeting JAK/STAT pathway in A549 NSCLC cells. These results indicated that astragalin drug could prove helpful in lung cancer treatment and research provided more in-vivo studies are performed.

摘要

本研究旨在探讨毛蕊异黄酮的抗肺癌作用。还进行了研究,以评估其对细胞凋亡诱导、ROS 产生、细胞迁移和侵袭以及 JAK/STAT3 信号通路的影响。MTT 法用于评估 NSCLC A549 细胞暴露于毛蕊异黄酮分子后细胞活力。使用 AO/EB 染色、彗星试验和 Western blot 试验研究细胞凋亡。荧光显微镜用于估计 ROS 产生。使用 Transwell 室试验测量细胞迁移和侵袭。使用 Western blot 试验研究毛蕊异黄酮对 JAK/STAT 通路的影响。结果表明,毛蕊异黄酮分子以剂量依赖的方式诱导 A549 细胞增殖抑制。此外,AO/EB 染色和 Western blot 试验表明,这种抗增殖作用是通过细胞凋亡介导的。毛蕊异黄酮调节 caspase-3、caspase-9、Bax、Bak、Cyt-c、Bcl-2、XIAP 和 Bcl-xL 的表达。毛蕊异黄酮诱导 A549 细胞的 DNA 损伤,这也表明细胞凋亡死亡。毛蕊异黄酮分子增强 A549 细胞的 ROS 产生。它以浓度依赖的方式抑制 A549 细胞的迁移和侵袭。最后,观察到毛蕊异黄酮药物在 A549 NSCLC 细胞中靶向 JAK/STAT 通路具有显著潜力。这些结果表明,毛蕊异黄酮药物在肺癌治疗和研究中可能会有所帮助,前提是进行更多的体内研究。

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