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利用同步辐射傅里叶变换红外显微镜、分子对接和体外研究探测硫酸化半乳糖对胆管癌细胞的抗癌活性。

Probing the Anti-Cancer Potency of Sulfated Galactans on Cholangiocarcinoma Cells Using Synchrotron FTIR Microspectroscopy, Molecular Docking, and In Vitro Studies.

机构信息

Department of Anatomy, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.

Department of Biochemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand.

出版信息

Mar Drugs. 2021 Apr 30;19(5):258. doi: 10.3390/md19050258.

DOI:10.3390/md19050258
PMID:33946151
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8145517/
Abstract

Sulfated galactans (SG) isolated from red alga have been reported to inhibit the growth of cholangiocarcinoma (CCA) cells, which was similar to the epidermal growth factor receptor (EGFR)-targeted drug, cetuximab. Herein, we studied the anti-cancer potency of SG compared to cetuximab. Biological studies demonstrated SG and cetuximab had similar inhibition mechanisms in CCA cells by down-regulating EGFR/ERK pathway, and the combined treatment induced a greater inhibition effect. The molecular docking study revealed that SG binds to the dimerization domain of EGFR, and this was confirmed by dimerization assay, which showed that SG inhibited ligand-induced EGFR dimer formation. Synchrotron FTIR microspectroscopy was employed to examine alterations in cellular macromolecules after drug treatment. The SR-FTIR-MS elicited similar spectral signatures of SG and cetuximab, pointing towards the bands of RNA/DNA, lipids, and amide I vibrations, which were inconsistent with the changes of signaling proteins in CCA cells after drug treatment. Thus, this study demonstrates the underlined anti-cancer mechanism of SG by interfering with EGFR dimerization. In addition, we reveal that FTIR signature spectra offer a useful tool for screening anti-cancer drugs' effect.

摘要

硫酸半乳聚糖(SG)从红藻中分离出来,据报道能抑制胆管癌(CCA)细胞的生长,这与表皮生长因子受体(EGFR)靶向药物西妥昔单抗相似。在此,我们研究了 SG 与西妥昔单抗相比的抗癌效力。生物学研究表明,SG 和西妥昔单抗通过下调 EGFR/ERK 通路在 CCA 细胞中有相似的抑制机制,联合治疗诱导了更大的抑制作用。分子对接研究表明 SG 结合到 EGFR 的二聚化结构域,这通过二聚化实验得到证实,该实验表明 SG 抑制配体诱导的 EGFR 二聚体形成。同步辐射傅里叶变换红外显微镜(SR-FTIR)用于检查药物处理后细胞大分子的变化。SR-FTIR-MS 产生了与 SG 和西妥昔单抗相似的光谱特征,指向 RNA/DNA、脂质和酰胺 I 振动带,这与 CCA 细胞在药物处理后信号蛋白的变化不一致。因此,本研究通过干扰 EGFR 二聚化证明了 SG 的潜在抗癌机制。此外,我们揭示了傅里叶变换红外光谱特征提供了一种用于筛选抗癌药物效果的有用工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d0/8145517/5154235ca4e9/marinedrugs-19-00258-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d0/8145517/2fda242e71e0/marinedrugs-19-00258-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d0/8145517/91dbfd7c3cc9/marinedrugs-19-00258-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d0/8145517/5cdd83f11e03/marinedrugs-19-00258-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d0/8145517/0dc21fc0d1f1/marinedrugs-19-00258-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d0/8145517/13c1677ff1d3/marinedrugs-19-00258-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d0/8145517/14cea7991ff6/marinedrugs-19-00258-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d0/8145517/4698f942d51a/marinedrugs-19-00258-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d0/8145517/5154235ca4e9/marinedrugs-19-00258-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d0/8145517/2fda242e71e0/marinedrugs-19-00258-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d0/8145517/91dbfd7c3cc9/marinedrugs-19-00258-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d0/8145517/5cdd83f11e03/marinedrugs-19-00258-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d0/8145517/0dc21fc0d1f1/marinedrugs-19-00258-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d0/8145517/13c1677ff1d3/marinedrugs-19-00258-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d0/8145517/14cea7991ff6/marinedrugs-19-00258-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d0/8145517/4698f942d51a/marinedrugs-19-00258-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d0/8145517/5154235ca4e9/marinedrugs-19-00258-g008.jpg

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