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SIRT1 表达通过上皮-间充质转化调节耐药性食管癌细胞的转化。

SIRT1 expression regulates the transformation of resistant esophageal cancer cells via the epithelial-mesenchymal transition.

机构信息

School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, PR China; Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, Henan, 450001, PR China.

School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, PR China; Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, Henan, 450001, PR China.

出版信息

Biomed Pharmacother. 2018 Jul;103:308-316. doi: 10.1016/j.biopha.2018.04.032. Epub 2018 Apr 24.

Abstract

Sirtuin1 (SIRT1) belongs to the mammalian sirtuin family and plays an important role in deacetylating histones and non-histones. SIRT1 is associated with tumor metastasis in several tumors. However, the effect of SIRT1 on the mechanism of metastasis in resistant esophageal cancer remains unclear. In this study, we demonstrated that increased migration and invasion in drug-resistant esophageal cancer cells (EC109/PTX, TE-1/PTX). Our experiments revealed that the selective SIRT1 inhibitor (EX527) significantly suppressed cells migrate and inhibited the occurrence of the epithelial-mesenchymal transition (EMT), thereby altering the invasiveness and metastatic potential of the esophageal cancer cell lines. In addition, we observed that the inhibition of SIRT1 could alter the expression of snail. In conclusion, these results indicate that SIRT1 may promote the transformation of tumor cells by inducing the EMT and may serve as a potential molecular target for the treatment of resistant esophageal cancer.

摘要

Sirtuin1(SIRT1)属于哺乳动物的 sirtuin 家族,在去乙酰化组蛋白和非组蛋白方面发挥着重要作用。SIRT1 与几种肿瘤的转移有关。然而,SIRT1 对耐药性食管癌转移机制的影响尚不清楚。在本研究中,我们证明了耐药性食管癌细胞(EC109/PTX、TE-1/PTX)中迁移和侵袭能力增加。我们的实验表明,选择性 SIRT1 抑制剂(EX527)可显著抑制细胞迁移并抑制上皮-间充质转化(EMT)的发生,从而改变食管癌细胞系的侵袭性和转移潜能。此外,我们观察到 SIRT1 的抑制可以改变 snail 的表达。总之,这些结果表明 SIRT1 可能通过诱导 EMT 促进肿瘤细胞的转化,并且可以作为治疗耐药性食管癌的潜在分子靶点。

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