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一种新型合成齐墩果酸衍生物通过调节细胞周期G2/M期阻滞抑制胶质瘤细胞增殖。

A Novel Synthetic Oleanolic Acid Derivative Inhibits Glioma Cell Proliferation by Regulating Cell Cycle G2/M Arrest.

作者信息

Tsai Tai-Hsin, Tsai Cheng-Yu, Moi Sin-Hua, Wu Chieh-Hsin, Lee Kuan-Ting, Hsu Yi-Chiang, Su Yu-Feng

机构信息

Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan.

Department of Surgery, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.

出版信息

Pharmaceuticals (Basel). 2023 Apr 24;16(5):642. doi: 10.3390/ph16050642.

Abstract

2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid-9,11-dihydro-trifluoroethyl amide (CDDO-dhTFEA) has antioxidant and anti-inflammatory activities; however, whether CDDO-dhTFEA has anticancer effects is unclear. The objective of this research was to investigate the possibility of CDDO-dhTFEA as a potential cancer-fighting treatment in glioblastoma cells. Our experiments were performed on U87MG and GBM8401 cells, and we found that CDDO-dhTFEA was effective in reducing cell proliferation in both cell lines, in a manner that was dependent on both time and concentration. Additionally, we observed that CDDO-dhTFEA had a significant impact on the regulation of cell proliferation, which was evident in the increase in DNA synthesis that was observed in both cell types. CDDO-dhTFEA induced G2/M cell cycle arrest and mitotic delay, which may be associated with the inhibition of proliferation. Treatment with CDDO-dhTFEA led to cell cycle G2/M arrest and inhibited proliferation of U87MG and GBM8401 cells by regulating G2/M cell cycle proteins and gene expression in GBM cells in vitro.

摘要

2-氰基-3,12-二氧代齐墩果-1,9(11)-二烯-28-酸-9,11-二氢-三氟乙酰胺(CDDO-dhTFEA)具有抗氧化和抗炎活性;然而,CDDO-dhTFEA是否具有抗癌作用尚不清楚。本研究的目的是探讨CDDO-dhTFEA作为胶质母细胞瘤细胞潜在抗癌治疗方法的可能性。我们在U87MG和GBM8401细胞上进行了实验,发现CDDO-dhTFEA在两种细胞系中均能有效降低细胞增殖,且其作用方式依赖于时间和浓度。此外,我们观察到CDDO-dhTFEA对细胞增殖的调节有显著影响,这在两种细胞类型中观察到的DNA合成增加中很明显。CDDO-dhTFEA诱导G2/M期细胞周期阻滞和有丝分裂延迟,这可能与增殖抑制有关。在体外,用CDDO-dhTFEA处理导致细胞周期G2/M期阻滞,并通过调节胶质母细胞瘤细胞中的G2/M期细胞周期蛋白和基因表达来抑制U87MG和GBM8401细胞的增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a33f/10222354/35c2edc9b099/pharmaceuticals-16-00642-g001.jpg

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