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金纳米粒子缀合 提取物对人肝癌细胞的抗转移作用。

Anti-Metastatic Effect of Gold Nanoparticle-Conjugated Extract on Human Hepatocellular Carcinoma Cells.

机构信息

Bio-IT Fusion Technology Research Institute, Pusan National University, Busan 609-735, Korea.

Department of Nanomaterials Engineering, Pusan National University, Busan 609-735, Korea.

出版信息

Int J Nanomedicine. 2020 Jul 27;15:5317-5331. doi: 10.2147/IJN.S246724. eCollection 2020.

DOI:10.2147/IJN.S246724
PMID:32904434
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7455757/
Abstract

PURPOSE

We aimed to study green-synthesized gold nanoparticles (GNPs) from (MT) root (MTR), stem (MTS), leaf (MTL), and fruit (MTF) extracts and evaluate their anti-metastatic properties in hepatocellular carcinoma cells. belongs to the Moraceae family and is widely used as a traditional medicinal plant given its biological activities.

METHODS

We quantified the phenolic and flavonoid contents, reducing capacity, and antioxidant activity of all four extracts. The facile and optimum synthesis of MT-GNPs was visualized using UV-vis spectra and dynamic light scattering (DLS). Surface morphology, selected area electron diffraction (SAED), and fast Fourier transform (FFT) pattern of MT-GNPs were assessed using high-resolution transmission electron microscopy (HR-TEM). The crystallized gold pattern of MT-GNPs was evaluated using energy dispersive spectroscopy (EDS) and X-ray diffraction (XRD). The functionalizing ligands of MT-extracts and MT-GNPs were determined using Fourier-transform infrared spectroscopy (FT-IR). The photocatalytic capabilities of MT-GNPs were assessed by measuring the reduction of rhodamine B and methylene blue. Cell viability assay was detected using Cell Counting Kit-8 solution. Anti-migratory and anti-invasive effects were assessed using cell migration and invasion assays. Matrix metalloproteinase (MMP)-9 and phospholipase D (PLD) enzymatic activities were measured using gelatin zymography and Amplex Red PLD assay, respectively. Western blotting and luciferase assay were used to detect protein expression.

RESULTS

All extracts had high phenolic and flavonoid contents and strong antioxidant and reducing capacities. Results from UV-Vis spectra, DLS, HR-TEM, EDS, XRD, and FT-IR showed the successful formation of MT-GNP with surface morphology, crystallinity, reduction capacity, capsulation, and stabilization. MTR-GNPs and MTS-GNPs had better catalytic activities than MTL-GNPs and MTF-GNPs for reduction of methylene blue and rhodamine B. Moreover, MTS-GNPs and MTR-GNPs exhibited the highest anti-migratory and anti-invasive potential and seemed to be more biologically active than the MTS and MTR extracts. Treatment with MT-GNPs decreased the enzymatic activity, translation levels of MMP-9 and PLD1. Our results showed that MTS-GNPs and MTR-GNPs could dramatically reverse transforming growth factor-β-induced vimentin and N-cadherin upregulation and E-cadherin downregulation.

CONCLUSION

The application of GNPs as a potential treatment approach for hepatocellular carcinoma can improve therapeutic efficiency.

摘要

目的

本研究旨在从 (MT)根(MTR)、茎(MTS)、叶(MTL)和果实(MTF)提取物中合成绿色金纳米粒子(GNPs),并评估其在肝癌细胞中的抗转移特性。 属于桑科,因其具有生物活性而被广泛用作传统药用植物。

方法

我们定量测定了四种提取物的酚类和类黄酮含量、还原能力和抗氧化活性。通过紫外-可见光谱和动态光散射(DLS)直观地观察 MT-GNPs 的简便和最佳合成。使用高分辨率透射电子显微镜(HR-TEM)评估 MT-GNPs 的表面形态、选区电子衍射(SAED)和快速傅里叶变换(FFT)模式。使用能量色散光谱(EDS)和 X 射线衍射(XRD)评估 MT-GNPs 的结晶金图案。使用傅里叶变换红外光谱(FT-IR)确定 MT-提取物和 MT-GNPs 的功能化配体。通过测量罗丹明 B 和亚甲基蓝的还原来评估 MT-GNPs 的光催化能力。使用细胞计数试剂盒-8 溶液检测细胞活力。通过细胞迁移和侵袭试验评估抗迁移和抗侵袭作用。使用明胶酶谱法和 Amplex Red PLD 测定法分别测量基质金属蛋白酶(MMP)-9 和磷脂酶 D(PLD)的酶活性。使用 Western blot 和荧光素酶测定法检测蛋白表达。

结果

所有提取物均具有较高的酚类和类黄酮含量以及较强的抗氧化和还原能力。紫外-可见光谱、DLS、HR-TEM、EDS、XRD 和 FT-IR 的结果表明,成功合成了具有表面形态、结晶度、还原能力、包裹和稳定化的 MT-GNP。MTR-GNPs 和 MTS-GNPs 对亚甲基蓝和罗丹明 B 的还原具有比 MTL-GNPs 和 MTF-GNPs 更好的催化活性。此外,MTS-GNPs 和 MTR-GNPs 表现出最高的抗迁移和抗侵袭潜力,似乎比 MTS 和 MTR 提取物更具生物活性。MT-GNPs 处理降低了 MMP-9 和 PLD1 的酶活性、翻译水平。我们的结果表明,MTS-GNPs 和 MTR-GNPs 可显著逆转转化生长因子-β诱导的波形蛋白和 N-钙黏蛋白上调以及 E-钙黏蛋白下调。

结论

将 GNPs 作为一种潜在的肝癌治疗方法的应用可以提高治疗效率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc8/7455757/d9f343a03e23/IJN-15-5317-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc8/7455757/9bbd0e4d43c0/IJN-15-5317-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc8/7455757/f17de4b93d2d/IJN-15-5317-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc8/7455757/dffd5c6229cc/IJN-15-5317-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc8/7455757/b06c686829c3/IJN-15-5317-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc8/7455757/c9090a512191/IJN-15-5317-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc8/7455757/d9f343a03e23/IJN-15-5317-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc8/7455757/9bbd0e4d43c0/IJN-15-5317-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc8/7455757/f17de4b93d2d/IJN-15-5317-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc8/7455757/dffd5c6229cc/IJN-15-5317-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc8/7455757/b06c686829c3/IJN-15-5317-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc8/7455757/c9090a512191/IJN-15-5317-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc8/7455757/d9f343a03e23/IJN-15-5317-g0006.jpg

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