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.
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.
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DOI：
10.1177/1533033820947485
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发表时间：
2020-01
影响因子：
2.8
通讯作者：
Luo Z
中科院分区：
文献类型：
--
作者：
Deng X;Chen C;Wu F;Qiu L;Ke Q;Sun R;Duan Q;Luo M;Luo Z
据报道，放射治疗会导致癌症转移。因此，必须开发新的放射治疗策略以避免这种副作用。将A549细胞暴露于辐射以诱导上皮-间充质转化（EMT）细胞模型。Real-time PCR和Western blotting检测mRNA和蛋白表达水平，Transwell侵袭实验和创伤愈合实验检测细胞迁移和侵袭能力。ELISA法检测可溶性E-钙粘蛋白（sE-cad）的分泌。siRNA用于沉默MMP 9表达。结果显示，A549 R细胞表现出EMT表型，E-钙粘蛋白、N-钙粘蛋白、Snail、Slug、波形蛋白和Twist表达增加，泛角蛋白表达减少。A549 R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A549 R和A549细胞的迁移和侵袭。相反，阻断sE-cad减弱了A549细胞的迁移和侵袭。姜黄素抑制sE-cad表达，逆转辐射诱导的EMT。此外，姜黄素抑制sE-cad增强的A549和A549 R细胞迁移和侵袭。姜黄素抑制MMP 9表达，沉默MMP 9抑制sE-cad表达。两者结合，我们发现了一个非经典的EMT现象引起的辐射。姜黄素通过降低MMP 9表达抑制辐射诱导的EMT和sE-cad表达来抑制NSCLC迁移和侵袭。
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.
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