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评价姜黄素纳米壳聚糖对 MCF-7、MDA-MB-231 和 SKBR3 细胞系中 miR-221 和 miR-222 表达及 Wnt/β-catenin 通路的影响。

Evaluating the effects of curcumin nano-chitosan on miR-221 and miR-222 expression and Wnt/β-catenin pathways in MCF-7, MDA-MB-231 and SKBR3 cell lines.

机构信息

Department of Anatomy, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

出版信息

Diagn Pathol. 2024 Feb 16;19(1):35. doi: 10.1186/s13000-024-01468-3.

Abstract

BACKGROUND

Breast cancer is one of the most common diseases worldwide that affects women of reproductive age. miR-221 and miR-222 are two highly homogeneous microRNAs that play pivotal roles in many cellular processes and regulate the Wnt/β-catenin signaling pathway. Curcumin (CUR), a yellow polyphenolic compound, targets numerous signaling pathways relevant to cancer therapy. The main aim of this study was to compare the ability of chitosan curcumin nanoparticle (CC-CUR) formulation with the curcumin in modulating miR-221 and miR-222 expression through Wnt/β-catenin signaling pathway in MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cell lines.

METHOD

Chitosan-cyclodextrin-tripolyphosphate containing curcumin nanoparticles (CC-CUR) were prepared. Cytotoxicity of the CUR and CC-CUR was evaluated. Experimental groups including CC-CUR, CUR and negative control were designed. The expression of miR-221 and miR-222 and Wnt/β-catenin pathway genes was measured.

RESULTS

The level of miR-221 and miR-222 and β-catenin genes decreased in MCF-7 and MDA-MB-231 cells and WIF1 gene increased in all cells in CC-CUR group. However, the results in SK-BR-3 cell line were unexpected; since miRs and WIF1 gene expressions were increased following CC-CUR administration and β-catenin decreased by administration of CUR.

CONCLUSION

Although the composite form of curcumin decreased the expression of miR-221 and miR-222 in MCF-7 and MDA cells, with significant decreasing of β-catenin and increasing of WIF1 gene in almost all three cell lines, we can conclude than this formulation exerts its effect mainly through the Wnt/β-catenin pathway. These preliminary findings may pave the way for the use of curcumin nanoparticles in the treatment of some known cancers.

摘要

背景

乳腺癌是全球最常见的疾病之一,影响生育期女性。miR-221 和 miR-222 是两种高度同源的 microRNAs,它们在许多细胞过程中发挥关键作用,并调节 Wnt/β-catenin 信号通路。姜黄素(CUR)是一种黄色多酚化合物,针对与癌症治疗相关的许多信号通路。本研究的主要目的是比较壳聚糖姜黄素纳米粒(CC-CUR)制剂与姜黄素通过 Wnt/β-catenin 信号通路在 MCF-7、MDA-MB-231 和 SK-BR-3 乳腺癌细胞系中调节 miR-221 和 miR-222 表达的能力。

方法

制备含有姜黄素的壳聚糖-环糊精-三聚磷酸酯纳米粒(CC-CUR)。评估 CUR 和 CC-CUR 的细胞毒性。设计 CC-CUR、CUR 和阴性对照组的实验组。测量 miR-221 和 miR-222 以及 Wnt/β-catenin 通路基因的表达。

结果

CC-CUR 组 MCF-7 和 MDA-MB-231 细胞中 miR-221 和 miR-222 以及β-catenin 基因水平降低,所有细胞中 WIF1 基因增加。然而,SK-BR-3 细胞系的结果出乎意料;CC-CUR 给药后 miRs 和 WIF1 基因表达增加,而 CUR 给药后 β-catenin 减少。

结论

尽管姜黄素的复合形式降低了 MCF-7 和 MDA 细胞中 miR-221 和 miR-222 的表达,但几乎所有三种细胞系中β-catenin 减少和 WIF1 基因增加,我们可以得出结论,这种制剂主要通过 Wnt/β-catenin 通路发挥作用。这些初步发现为使用姜黄素纳米粒治疗某些已知癌症铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4465/10870642/d2566d8c5208/13000_2024_1468_Fig1_HTML.jpg

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