多组学分析揭示五味子木脂素和肌苷通过ERK1/2通路影响肝癌细胞EMT的机制

IF 3.9 4区 生物学 Q1 GENETICS & HEREDITY
Jingjing Jiang, Ru Cheng, Aoqi Song, Yuefen Lou, Guorong Fan
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引用次数: 0

摘要

背景:肝细胞癌(HCC)是一种全球常见的癌症,通常发病较晚,对化疗的耐药性强,导致治疗效果不理想。中药成分的抗癌作用已得到公认:目的:探讨五味子木脂素和肌苷通过细胞外信号调节激酶(ERK)1/2途径抑制肝癌细胞上皮-间质转化(EMT)的机制,并通过多组学鉴定生物标志物、分子亚型和靶点,以实现精准肿瘤学:方法:使用细胞计数试剂盒-8(CCK-8)测定法评估细胞增殖情况,使用划痕法和透孔法评估侵袭和迁移情况。流式细胞术量化了细胞凋亡率。实时 PCR 和 Western 印迹分析了 CCL20、p-ERK1/2、c-Myc、Vimentin 和 E-cadherin/N-cadherin 的表达水平。用特定公式计算肿瘤体积和生长情况:结果:五味子木脂素和肌苷的组合能以剂量和时间依赖性的方式降低 CCL20 的表达,抑制肝癌的增殖和迁移,并增强其凋亡。分子分析表明,E-cadherin 增加,N-cadherin、p-ERK1/2、c-Myc 和 Vimentin 表达减少,表明 ERK1/2 通路受到调节。在体内,经处理的裸鼠显示肿瘤生长和体积明显缩小:结论:五味子木脂素和肌苷可通过ERK1/2通路抵消CCL20诱导的肝癌细胞EMT、侵袭和迁移,并促进细胞凋亡。多组学分析可进一步帮助确定癌症精准治疗的新型生物标记物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Multi-omics analysis reveals mechanism of Schisandra chinensis lignans and acteoside on EMT in hepatoma cells via ERK1/2 pathway

Multi-omics analysis reveals mechanism of Schisandra chinensis lignans and acteoside on EMT in hepatoma cells via ERK1/2 pathway

Background

Hepatocellular carcinoma (HCC), a globally common cancer, often presents late and shows high resistance to chemotherapy, resulting in suboptimal treatment efficacy. Components from traditional Chinese medicines have been recognized for their anti-cancer properties.

Objective

Exploring the mechanism of Schisandra chinensis lignans and acteoside in suppressing Epithelial-Mesenchymal Transition (EMT) in hepatoma cells through the Extracellular signal-Regulated Kinases (ERK)1/2 pathway and identifying biomarkers, molecular subtypes, and targets via multi-omics for precision oncology.

Methods

Proliferation was assessed using cell counting kit-8 (CCK-8) assays, with scratch and transwell assays for evaluating invasion and migration. Flow cytometry quantified apoptosis rates. Expression levels of CCL20, p-ERK1/2, c-Myc, Vimentin, and E-cadherin/N-cadherin were analyzed by real-time PCR and Western blot. Tumor volume was calculated with a specific formula, and growth.

Results

The Schisandra chinensis lignans and acteoside combination decreased CCL20 expression, inhibited hepatoma proliferation and migration, and enhanced apoptosis in a dose- and time-dependent manner. Molecular analysis revealed increased E-cadherin and decreased N-cadherin, p-ERK1/2, c-Myc, and Vimentin expression, indicating ERK1/2 pathway modulation. In vivo, treated nude mice showed significantly reduced tumor growth and volume.

Conclusion

Schisandra chinensis lignans and acteoside potentially counteract CCL20-induced EMT, invasion, and migration in hepatocellular carcinoma cells via the ERK1/2 pathway, enhancing apoptosis. Multi-omics analysis further aids in pinpointing novel biomarkers for precision cancer therapy.

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来源期刊
CiteScore
3.50
自引率
3.40%
发文量
92
审稿时长
2 months
期刊介绍: Functional & Integrative Genomics is devoted to large-scale studies of genomes and their functions, including systems analyses of biological processes. The journal will provide the research community an integrated platform where researchers can share, review and discuss their findings on important biological questions that will ultimately enable us to answer the fundamental question: How do genomes work?
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