欧克珊酮通过靶向miR-199a-5p/E2F3调控轴抑制肝细胞癌进展

IF 3 4区 医学 Q3 CHEMISTRY, MEDICINAL
Ahmed Abdullah Al Awadh
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引用次数: 0

摘要

背景:肝细胞癌(HCC)是全球范围内癌症相关死亡的主要原因之一。本研究旨在评估欧克山酮对肝癌细胞系增殖的影响,并阐明其潜在的分子机制。方法:培养肝癌细胞株HepG2、Huh-7、SNU-398、SK-HEP-1、Hep3B和正常肝细胞株THLE-2,并用浓度为0 ~ 100 μM的欧克山酮处理。使用MTT法评估细胞活力,同时使用相差显微镜和细胞周期分析来评估形态学变化和细胞周期分布。利用qRT-PCR测量miRNA和mRNA的表达水平,而双荧光素酶报告基因试验验证了miR-199a-5p和E2F3之间的相互作用。结果:欧克蒽酮显著(P < 0.05)抑制了所有HCC细胞系的细胞增殖,IC₂就声压值在6.25 - 25 μM之间。HepG2细胞表现出了显著的灵敏度,IC₂´´´为6.25 μM。欧克山酮诱导G1期阻滞,其特征是Cyclin D1和E的表达降低,p21水平升高。此外,它上调miR-199a-5p, miR-199a-5p通过靶向E2F3被确定为抗增殖作用的中介。在伤口愈合实验中,欧克山酮也显著抑制HepG2细胞的迁移(P < 0.05)。结论:综上所述,欧克山酮通过miR-199a-5p-E2F3轴对HCC细胞发挥抗增殖作用,抑制细胞迁移。这些发现支持其作为HCC治疗剂的潜力,强调需要进一步研究其临床应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Euxanthone Inhibits Hepatocellular Carcinoma Progression by Targeting the miR-199a-5p/E2F3 Regulatory Axis.

Background: Hepatocellular carcinoma (HCC) ranks among the leading causes of cancer-related deaths on a global scale. This study aimed to evaluate the effects of euxanthone on the proliferation of HCC cell lines and elucidate the underlying molecular mechanisms.

Methods: HCC cell lines (HepG2, Huh-7, SNU-398, SK-HEP-1, Hep3B) and the normal liver cell line THLE-2 were cultured and treated with euxanthone at concentrations between 0 and 100 μM. Cell viability was evaluated using the MTT assay, while phase contrast microscopy and cell cycle analysis were performed to evaluate morphological changes and cell cycle distribution. qRT-PCR was utilized to measure miRNA and mRNA expression levels, while a dual luciferase reporter assay validated the interaction between miR-199a-5p and E2F3.

Results: Euxanthone significantly (P < 0.05) inhibited cell proliferation in all HCC cell lines, with IC₂⁽ values between 6.25 and 25 μM. HepG2 cells exhibited pronounced sensitivity, with an IC₂⁽ of 6.25 μM. Euxanthone induced a G1 phase arrest, characterized by decreased expression of Cyclin D1 and E, and increased levels of p21. Additionally, it upregulated miR-199a-5p, which was identified as a mediator of the antiproliferative effects by targeting E2F3. Euxanthone treatment also significantly (P < 0.05) inhibited HepG2 cell migration in a wound healing assay.

Conclusion: Taken together, euxanthone exerts antiproliferative effects on HCC cells via the miR-199a-5p-E2F3 axis and inhibits cell migration. These findings support its potential as a therapeutic agent for HCC, highlighting the need for further investigation into its clinical applications.

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来源期刊
Anti-cancer agents in medicinal chemistry
Anti-cancer agents in medicinal chemistry ONCOLOGY-CHEMISTRY, MEDICINAL
CiteScore
5.10
自引率
3.60%
发文量
323
审稿时长
4-8 weeks
期刊介绍: Formerly: Current Medicinal Chemistry - Anti-Cancer Agents. Anti-Cancer Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of anti-cancer agents. Each issue contains a series of timely in-depth reviews and guest edited issues written by leaders in the field covering a range of current topics in cancer medicinal chemistry. The journal only considers high quality research papers for publication. Anti-Cancer Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cancer drug discovery.
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