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吲哚美辛通过拉曼光谱预防转化生长因子-β诱导的胰腺癌上皮间质转化。

Indomethacin prevents TGF-β-induced epithelial-to-mesenchymal transition in pancreatic cancer cells; evidence by Raman spectroscopy.

机构信息

Department of Pharmacology, Faculty of Medicine, University of Erciyes, Kayseri, Turkiye; Genkok Genome and Stem Cell Centre, University of Erciyes, Kayseri, Turkiye.

Department of Materials Science and Engineering, University of Erciyes, Kayseri, Turkiye; ERNAM - Nanotechnology Application and Research Center, University of Erciyes, Kayseri, Turkiye.

出版信息

Spectrochim Acta A Mol Biomol Spectrosc. 2022 Nov 5;280:121493. doi: 10.1016/j.saa.2022.121493. Epub 2022 Jun 16.

DOI:10.1016/j.saa.2022.121493
PMID:35728400
Abstract

Pancreatic ductal adenocarcinoma (PDAC) has a very low survival rate due to the late detection and poor response to chemotherapy. Epithelial-to-mesenchymal transition (EMT) is considered an important step in tumor progression with regard to invasion and metastasis, and Transforming Growth Factor-beta (TGF-β) signaling has been shown to play an important role in EMT. Therefore, we aimed to investigate whether indomethacin, an anti-inflammatory and analgesic drug, has any effect on TGF-β-induced EMT in pancreatic cancer cell line and analyze the changes in their molecular structures by Raman spectroscopy and other molecular techniques. Indomethacin treated Panc-1 cells were analyzed with Raman spectroscopy, quantitative polymerase chain reaction and immunofluorescence techniques after the induction of EMT with TGF-β. The exposure of Panc-1 cells to TGF-β resulted in characteristic morphological alterations of EMT, and indomethacin inhibits TGF-β-induced EMT through up-regulation of E-cadherin and down-regulation of N-cadherin and Snail expressions. Raman spectroscopy supported by principal component analysis (PCA) confirmed the effects of both TGF-β and indomethacin. Raman spectra were further analyzed using the PCA-assisted vector machine algorithm and it was seen that the data could be classified with 97.6% accuracy. Our results suggest that indomethacin may have a significant effect on PDAC metastasis, and Raman spectroscopy was able to probe EMT-related changes and the efficacy of indomethacin in a short time and without the need for specific reagents compared to other molecular techniques.

摘要

胰腺导管腺癌 (PDAC) 由于检测较晚和对化疗反应不佳,生存率非常低。上皮间质转化 (EMT) 被认为是肿瘤进展中侵袭和转移的重要步骤,转化生长因子-β (TGF-β) 信号已被证明在 EMT 中发挥重要作用。因此,我们旨在研究非甾体抗炎药吲哚美辛是否对胰腺癌细胞系中 TGF-β 诱导的 EMT 有影响,并通过拉曼光谱和其他分子技术分析其分子结构的变化。用 TGF-β 诱导 EMT 后,用拉曼光谱、定量聚合酶链反应和免疫荧光技术分析吲哚美辛处理的 Panc-1 细胞。TGF-β 暴露导致 EMT 的特征形态改变,吲哚美辛通过上调 E-钙粘蛋白和下调 N-钙粘蛋白和 SNAIL 表达来抑制 TGF-β 诱导的 EMT。基于主成分分析 (PCA) 的拉曼光谱证实了 TGF-β 和吲哚美辛的作用。进一步使用 PCA 辅助向量机算法分析拉曼光谱,结果表明数据可以以 97.6%的准确率进行分类。我们的结果表明,吲哚美辛可能对 PDAC 转移有显著影响,与其他分子技术相比,拉曼光谱能够在短时间内探测 EMT 相关变化和吲哚美辛的疗效,而无需特定试剂。

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