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合成异甘草素通过其抗氧化机制抑制人舌鳞状癌细胞。

Synthetic Isoliquiritigenin Inhibits Human Tongue Squamous Carcinoma Cells through Its Antioxidant Mechanism.

作者信息

Hou Cuilan, Li Wenguang, Li Zengyou, Gao Jing, Chen Zhenjie, Zhao Xiqiong, Yang Yaya, Zhang Xiaoyu, Song Yong

机构信息

School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province 730000, China; Key Lab of Preclinical Study for New Drugs of Gansu Province, Lanzhou, Gansu Province 730000, China; Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai 200000, China.

School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province 730000, China; Key Lab of Preclinical Study for New Drugs of Gansu Province, Lanzhou, Gansu Province 730000, China.

出版信息

Oxid Med Cell Longev. 2017;2017:1379430. doi: 10.1155/2017/1379430. Epub 2017 Jan 22.

Abstract

Isoliquiritigenin (ISL), a natural antioxidant, has antitumor activity in different types of cancer cells. However the antitumor effect of ISL on human tongue squamous carcinoma cells (TSCC) is not clear. Here we aimed to investigate the effects of synthetic isoliquiritigenin (S-ISL) on TSCC and elucidate the underlying mechanisms. S-ISL was synthesized and elucidated from its nuclear magnetic resonance spectrum and examined using high performance liquid chromatography. The effects of S-ISL on TSCC cells (Tca8113) were evaluated in relation to cell proliferation, apoptosis and adhesion, migration, and invasion using sulforhodamine B assay, fluorescence microscopy technique, flow cytometry (FCM) analysis, and Boyden chamber assay. The associated regulatory mechanisms were examined using FCM and fluorescence microscopy for intracellular reactive oxygen species (ROS) generation, Gelatin zymography assay for matrix metalloproteinase (MMP) activities, and Western blot for apoptosis regulatory proteins (Bcl-2 and Bax). Our data indicated that S-ISL inhibited Tca8113 cell proliferation, adhesion, migration, and invasion while promoting the cell apoptosis. Such effects were accompanied by downregulation of Bcl-2 and upregulation of Bax, reduction of MMP-2 and MMP-9 activities, and decreased ROS production. We conclude that S-ISL is a promising agent targeting TSCC through multiple anticancer effects, regulated by its antioxidant mechanism.

摘要

异甘草素(ISL)是一种天然抗氧化剂,在不同类型的癌细胞中具有抗肿瘤活性。然而,ISL对人舌鳞状细胞癌(TSCC)细胞的抗肿瘤作用尚不清楚。在此,我们旨在研究合成异甘草素(S-ISL)对TSCC的影响,并阐明其潜在机制。通过核磁共振谱合成并鉴定了S-ISL,并使用高效液相色谱法进行检测。使用磺酰罗丹明B测定法、荧光显微镜技术、流式细胞术(FCM)分析和博伊登室测定法,评估S-ISL对TSCC细胞(Tca8113)的细胞增殖、凋亡以及黏附、迁移和侵袭的影响。使用FCM和荧光显微镜检查细胞内活性氧(ROS)生成的相关调节机制,使用明胶酶谱法检测基质金属蛋白酶(MMP)活性,使用蛋白质免疫印迹法检测凋亡调节蛋白(Bcl-2和Bax)。我们的数据表明,S-ISL抑制Tca8113细胞的增殖、黏附、迁移和侵袭,同时促进细胞凋亡。这些作用伴随着Bcl-2的下调和Bax的上调、MMP-2和MMP-9活性的降低以及ROS产生的减少。我们得出结论,S-ISL是一种有前景的靶向TSCC的药物,通过多种抗癌作用发挥作用,并受其抗氧化机制调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0765/5292127/34deb78ecd63/OMCL2017-1379430.001.jpg

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