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表柔比星通过调控miRNA-143-3p/Bcl-2 轴抑制食管鳞癌细胞的增殖、侵袭和迁移。

Epinodosin suppresses the proliferation, invasion, and migration of esophageal squamous cell carcinoma by mediating miRNA-143-3p/Bcl-2 axis.

机构信息

Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China.

Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.

出版信息

Phytother Res. 2023 Nov;37(11):5378-5393. doi: 10.1002/ptr.7978. Epub 2023 Aug 17.

DOI:10.1002/ptr.7978
PMID:37589332
Abstract

Epinodosin has shown antibacterial and antitumor biological characteristics in the documents. We found that Epinodosin has an effective inhibitory effect on esophageal squamous cell carcinoma (ESCC). However, the potential roles and mechanisms of Epinodosin in ESCC remain unclear. We performed many experiments to clarify the effect and mechanism of Epinodosin on ESCC. In this study, cell viability, invasion, migration, and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,-diphenytetrazoliumromide (MTT), Transwell, and flow cytometry. The differentially expressed miRNAs were screened through RNA transcriptome sequencing. The expression levels of miRNA-143-3p and some proteins were measured by real-time polymerase chain reaction (PCR) and Western blot. The anticancer effects of Epinodosin in vivo were determined by a nude mouse model. Epinodosin suppressed cell proliferation/invasion/migration and induced ESCC cell apoptosis. Epinodosin remarkably affected the protein expression of mitogen-activated protein kinase (MAPK) signaling pathway. The animal experiments demonstrated that Epinodosin could attenuate the growth of ESCC tumors in nude mice. The expression of p53, Bim, and Bax was upregulated, while that of Bcl-2 was downregulated in tumor tissues. In conclusion, Epinodosin suppresses cell viability/invasion/migration, while induces ESCC cell apoptosis by mediating miRNA-143-3p and Bcl-2, and can markedly attenuate the growth of ESCC tumors in nude mice.

摘要

恩比霉素在文献中表现出抗菌和抗肿瘤的生物特性。我们发现恩比霉素对食管鳞癌(ESCC)具有有效的抑制作用。然而,恩比霉素在 ESCC 中的潜在作用和机制尚不清楚。我们进行了许多实验来阐明恩比霉素对 ESCC 的作用和机制。在这项研究中,通过 3-(4,5-二甲基-2-噻唑基)-2,-二苯基四氮唑溴盐(MTT)、Transwell 和流式细胞术测定细胞活力、侵袭、迁移和凋亡。通过 RNA 转录组测序筛选差异表达的 miRNA。通过实时聚合酶链反应(PCR)和 Western blot 测量 miRNA-143-3p 和一些蛋白质的表达水平。通过裸鼠模型确定恩比霉素在体内的抗癌作用。恩比霉素抑制细胞增殖/侵袭/迁移并诱导 ESCC 细胞凋亡。恩比霉素显着影响丝裂原活化蛋白激酶(MAPK)信号通路的蛋白表达。动物实验表明,恩比霉素可减轻裸鼠 ESCC 肿瘤的生长。肿瘤组织中 p53、Bim 和 Bax 的表达上调,而 Bcl-2 的表达下调。总之,恩比霉素通过调节 miRNA-143-3p 和 Bcl-2 抑制细胞活力/侵袭/迁移,诱导 ESCC 细胞凋亡,并能显著减轻裸鼠 ESCC 肿瘤的生长。

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