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白头翁汤通过miR-495-3p/BUB1/STAT3轴抑制食管癌细胞生长。

Baitouweng decoction suppresses growth of esophageal carcinoma cells through miR-495-3p/BUB1/STAT3 axis.

作者信息

Yang Hui, Chen Xiao-Wei, Song Xue-Jie, Du Hai-Yang, Si Fu-Chun

机构信息

Henan Key Laboratory of Traditional Chinese Medicine Syndrome and Prescription in Signaling, Henan International Joint Laboratory of TCM Syndrome and Prescription in Signaling, Traditional Chinese Medicine School, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China.

出版信息

World J Gastrointest Oncol. 2024 Jul 15;16(7):3193-3210. doi: 10.4251/wjgo.v16.i7.3193.

DOI:10.4251/wjgo.v16.i7.3193
PMID:39072160
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11271792/
Abstract

BACKGROUND

Esophageal carcinoma (EC) is one of the most prevalent cancers in human populations worldwide. Baitouweng decoction is one of the most important Chinese medicine formulas, with the potential to treat cancer.

AIM

To investigate the role and mechanism of Baitouweng decoction on EC cells.

METHODS

Differentially expressed genes (DEGs) in EC tissues and normal tissues were screened by the cDNA microarray technique and by bioinformatics methods. The target genes of microRNAs were predicted based on the TargetScan database and verified by dual luciferase gene reporter assay. We used Baitouweng decoction to intervene EC cells, and detected the activity of EC9706 and KYSE150 cells by the MTT method. Cell cycle and apoptosis were measured by flow cytometry. The expression of mRNA and miR-495-3p was measured by qRT-PCR. The protein levels of BUB1, STAT3, p-STAT3, CCNB1, CDK1, Bax, Caspase3, and Caspase9 were measured by Western blot analysis. The migration and invasion abilities of the cells were measured by wound-healing assay and Transwell invasion assay, respectively.

RESULTS

DEGs identified are involved in biological processes, signaling pathways, and network construction, which are mainly related to mitosis. was the key hub gene, and it is also a target gene of miR-495-3p. Baitouweng decoction could upregulate miR-495-3p and inhibit expression. experiments showed that Baitouweng decoction significantly inhibited the migration and invasion of EC cells and induced apoptosis and G2/M phase arrest. After treatment with Baitouweng decoction, the expression of Bax, Caspase 3, and Caspase 9 in EC cells increased significantly, while the expression of BUB1, CCNB1, and CDK1 decreased significantly. Moreover, the STAT3 signaling pathway may play an important role in this process.

CONCLUSION

Baitouweng decoction has a significant inhibitory effect on EC cell growth. BUB1 is a potential therapeutic target for EC. Further analysis showed that Baitouweng decoction may inhibit the growth of EC cells by upregulating miR-495-3p targeting the BUB1-mediated STAT3 signal pathway.

摘要

背景

食管癌(EC)是全球人类中最常见的癌症之一。白头翁汤是最重要的中药方剂之一,具有治疗癌症的潜力。

目的

探讨白头翁汤对食管癌细胞的作用及机制。

方法

采用cDNA微阵列技术和生物信息学方法筛选食管癌组织和正常组织中的差异表达基因(DEGs)。基于TargetScan数据库预测微小RNA的靶基因,并通过双荧光素酶基因报告试验进行验证。我们用白头翁汤干预食管癌细胞,采用MTT法检测EC9706和KYSE150细胞的活性。通过流式细胞术检测细胞周期和凋亡情况。采用qRT-PCR检测mRNA和miR-495-3p的表达。通过蛋白质印迹分析检测BUB1、STAT3、p-STAT3、CCNB1、CDK1、Bax、Caspase3和Caspase9的蛋白水平。分别采用伤口愈合试验和Transwell侵袭试验检测细胞的迁移和侵袭能力。

结果

鉴定出的差异表达基因参与生物过程、信号通路和网络构建,主要与有丝分裂相关。 是关键枢纽基因,也是miR-495-3p的靶基因。白头翁汤可上调miR-495-3p并抑制 表达。 实验表明,白头翁汤显著抑制食管癌细胞的迁移和侵袭,并诱导凋亡和G2/M期阻滞。用白头翁汤处理后,食管癌细胞中Bax、Caspase 3和Caspase 9的表达显著增加,而BUB1、CCNB1和CDK1的表达显著降低。此外,STAT3信号通路可能在此过程中起重要作用。

结论

白头翁汤对食管癌细胞生长具有显著抑制作用。BUB1是食管癌的潜在治疗靶点。进一步分析表明,白头翁汤可能通过上调靶向BUB1介导的STAT3信号通路的miR-495-3p来抑制食管癌细胞的生长。

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本文引用的文献

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Baitouweng decoction alleviates dextran sulfate sodium-induced ulcerative colitis by suppressing leucine-related mTORC1 signaling and reducing oxidative stress.白头翁汤通过抑制亮氨酸相关的 mTORC1 信号和减少氧化应激来缓解葡聚糖硫酸钠诱导的溃疡性结肠炎。
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New Baitouweng decoction combined with fecal microbiota transplantation alleviates DSS-induced colitis in rats by regulating gut microbiota metabolic homeostasis and the STAT3/NF-κB signaling pathway.新白头翁汤联合粪菌移植通过调节肠道微生物群代谢稳态和 STAT3/NF-κB 信号通路缓解 DSS 诱导的大鼠结肠炎。
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