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姜黄素通过抑制辐射诱导的上皮-间充质转化和可溶性 E-钙黏蛋白表达抑制非小细胞肺癌细胞的迁移和侵袭。

Curcumin Inhibits the Migration and Invasion of Non-Small-Cell Lung Cancer Cells Through Radiation-Induced Suppression of Epithelial-Mesenchymal Transition and Soluble E-Cadherin Expression.

机构信息

Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China.

HubeiKey Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China.

出版信息

Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820947485. doi: 10.1177/1533033820947485.

Abstract

Radiotherapy has been reported to cause cancer metastasis. Thus, a new strategy for radiotherapy must be developed to avoid this side effect. A549 cells were exposed to radiation to induce an epithelial-mesenchymal transition (EMT) cell model. Real-time PCR and western blotting were used to detect mRNA and protein expression levels, and Transwell invasion and wound healing assays were used to detect cell migration and invasion. ELISA was used to detect soluble E-cadherin (sE-cad) secretion. siRNA was used to silence MMP9 expression. The results show that A549R cells exhibited an EMT phenotype with increased E-cadherin, N-cadherin, Snail, Slug, vimentin and Twist expression and decreased pan-keratin expression. sE-cad levels were increased in A549R cells and in the serum of NSCLC patients with distant metastasis. Exogenous sE-cad treatment and sE-cad overexpression promoted A549R and A549 cell migration and invasion. In contrast, blocking sE-cad attenuated A549 cell migration and invasion. Curcumin inhibited sE-cad expression and reversed EMT induced by radiation. Furthermore, curcumin suppressed sE-cad-enhanced A549 and A549R cell migration and invasion. Curcumin inhibited MMP9 expression, and silencing MMP9 suppressed sE-cad expression. Taken together, we found a nonclassic EMT phenomenon induced by radiation. Curcumin inhibits NSCLC migration and invasion by suppressing radiation-induced EMT and sE-cad expression by decreasing MMP9 expression.

摘要

放疗被报道可引起癌症转移。因此,必须开发新的放疗策略以避免这种副作用。将 A549 细胞暴露于辐射下以诱导上皮-间充质转化(EMT)细胞模型。实时 PCR 和 Western blot 用于检测 mRNA 和蛋白表达水平,Transwell 侵袭和划痕愈合实验用于检测细胞迁移和侵袭。ELISA 用于检测可溶性 E-钙黏蛋白(sE-cad)分泌。siRNA 用于沉默 MMP9 表达。结果显示,A549R 细胞表现出 EMT 表型,E-钙黏蛋白、N-钙黏蛋白、Snail、Slug、波形蛋白和 Twist 表达增加,pan-角蛋白表达减少。A549R 细胞和有远处转移的 NSCLC 患者血清中 sE-cad 水平升高。外源性 sE-cad 处理和 sE-cad 过表达促进 A549R 和 A549 细胞迁移和侵袭。相反,阻断 sE-cad 可减弱 A549 细胞的迁移和侵袭。姜黄素抑制 sE-cad 表达并逆转辐射诱导的 EMT。此外,姜黄素抑制 sE-cad 增强的 A549 和 A549R 细胞迁移和侵袭。姜黄素抑制 MMP9 表达,沉默 MMP9 抑制 sE-cad 表达。综上所述,我们发现了一种由辐射诱导的非经典 EMT 现象。姜黄素通过抑制辐射诱导的 EMT 和 MMP9 表达降低 sE-cad 表达来抑制 NSCLC 的迁移和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/904e/7607721/dc92eec8d34f/10.1177_1533033820947485-fig1.jpg

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