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黄芩素,一种中药,通过激活 SIRT1/AMPK 信号通路抑制人非小细胞肺癌(NSCLC)细胞 A549 和 H1299 的增殖和迁移。

Baicalin, a Chinese Herbal Medicine, Inhibits the Proliferation and Migration of Human Non-Small Cell Lung Carcinoma (NSCLC) Cells, A549 and H1299, by Activating the SIRT1/AMPK Signaling Pathway.

机构信息

Department of Thoracic Surgery, Fenghua Peoples' Hospital of Ningbo City, Ningbo, Zhejiang, China (mainland).

Department of Thoracic Surgery, The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, Zhejiang, China (mainland).

出版信息

Med Sci Monit. 2018 Apr 10;24:2126-2133. doi: 10.12659/msm.909627.

Abstract

BACKGROUND Baicalin is a flavonoid derived from Scutellaria baicalensis, used in Chinese herbal medicine. Activation of the sirtuin 1 gene (SIRT1) and adenosine monophosphate (AMP)-activated protein kinase gene (AMPK), the SIRT1/AMPK signaling pathway, is associated with human malignant tumors. The aim of this study was to investigate the effects of baicalin on the cell viability, apoptosis, proliferation, and migration of human non-small cell lung cancer (NSCLC) cells, A549 and H1299, in vitro. MATERIAL AND METHODS Human NSCLC cells, A549 and H1299, were treated with serial doses of baicalin. Small interfering RNA (siRNA) silencing of the SIRT1 and AMPK genes was performed using cell transfection. The MTT assay was used to determine cell viability, flow cytometry was used to measure cell apoptosis, wound healing and transwell assays were used to assess cell migration of A549 and H1299 cells. Western blotting was used to measure protein expression and phosphorylation levels in untreated A549 and H1299 cells, and cells treated with increasing doses of baicalin. RESULTS Baicalin inhibited the viability, migration, and invasion of A549 and H1299 cells, and increased cell apoptosis in a dose-dependent manner. Baicalin activated the SIRT1/AMPK and mechanistic target of rapamycin (mTOR), and SIRT1/AMPK and matrix metalloproteinase (MMP) signaling in A549 and H1299 cells in a dose-dependent manner. siRNA silencing of SIRT1 and AMPK reduced the effects of baicalin on cell proliferation and migration. CONCLUSIONS Baicalin, a flavonoid used in Chinese herbal medicine, inhibited the proliferation and migration of human NSCLC cells, A549 and H1299, by activating the SIRT1/AMPK signaling pathway.

摘要

背景

黄芩苷是一种从黄芩中提取的黄酮类化合物,用于中药。Sirtuin 1 基因(SIRT1)和腺苷单磷酸(AMP)激活的蛋白激酶基因(AMPK)的激活,与人类恶性肿瘤有关。本研究旨在探讨黄芩苷对体外人非小细胞肺癌(NSCLC)细胞 A549 和 H1299 的细胞活力、凋亡、增殖和迁移的影响。

材料和方法

用黄芩苷处理人非小细胞肺癌细胞 A549 和 H1299。采用细胞转染沉默 SIRT1 和 AMPK 基因的小干扰 RNA(siRNA)。MTT 法测定细胞活力,流式细胞术测定细胞凋亡,划痕愈合和 Transwell 测定 A549 和 H1299 细胞迁移。Western blot 法测定未经处理的 A549 和 H1299 细胞以及用不同剂量黄芩苷处理的细胞中的蛋白表达和磷酸化水平。

结果

黄芩苷呈剂量依赖性抑制 A549 和 H1299 细胞的活力、迁移和侵袭,并增加细胞凋亡。黄芩苷在 A549 和 H1299 细胞中呈剂量依赖性激活 SIRT1/AMPK 和雷帕霉素靶蛋白(mTOR),以及 SIRT1/AMPK 和基质金属蛋白酶(MMP)信号通路。SIRT1 和 AMPK 的 siRNA 沉默降低了黄芩苷对细胞增殖和迁移的影响。

结论

作为中药的一种黄酮类化合物,黄芩苷通过激活 SIRT1/AMPK 信号通路抑制人非小细胞肺癌细胞 A549 和 H1299 的增殖和迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2d5/5909419/a87cde3bd7c2/medscimonit-24-2126-g001.jpg

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