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乙酰水杨酸对皮肤和葡萄膜黑色素瘤细胞系具有强大的抗肿瘤和抗血管生成作用。

Acetylsalicylic Acid Exerts Potent Antitumor and Antiangiogenic Effects in Cutaneous and Uveal Melanoma Cell Lines.

作者信息

Fausto de Souza Dominique, Tsering Thupten, Burnier Miguel N, Bravo-Filho Vasco, Dias Ana Beatriz Toledo, Abdouh Mohamed, Goyeneche Alicia, Burnier Julia Valdemarin

机构信息

Henry C. Witelson Ocular Pathology Laboratory, McGill University, Montreal, Québec, Canada.

出版信息

Ocul Oncol Pathol. 2020 Dec;6(6):442-455. doi: 10.1159/000510582. Epub 2020 Nov 4.

Abstract

INTRODUCTION

Acetylsalicylic acid (ASA) has been investigated for a potential anticancer role in several cancers, such as colorectal, ovarian, and endometrial cancer. Moreover, ASA has been shown to abrogate various processes that contribute to tumor growth and progression.

OBJECTIVE

The aim of this study was to evaluate the effects of ASA on cutaneous melanoma (CM) and uveal melanoma (UM).

METHODS

Human CM and UM cells were treated with 5 mM ASA and assessed for changes in cellular functions. Antiangiogenic effects of ASA were determined using an ELISA-based assay for 10 proangiogenic cytokines, and then validated by Western blot. Finally, proteomic analysis of ASA-treated cells was performed to elucidate the changes that may be responsible for ASA-mediated effects in melanoma cells.

RESULTS

Treatment with ASA significantly inhibited the proliferation, invasion, and migration capabilities, and caused a significant decrease in angiogenin and PIGF secretion in both CM and UM. Mass spectrometry revealed 179 protein changes associated with ASA in the CM and UM cell lines.

CONCLUSIONS

These results suggest that ASA may be effective as an adjuvant therapy in metastatic CM and UM. Future studies are needed to determine the regulating targets that are responsible for the antitumor effects of ASA.

摘要

引言

乙酰水杨酸(ASA)已在多种癌症中被研究其潜在的抗癌作用,如结直肠癌、卵巢癌和子宫内膜癌。此外,ASA已被证明可消除多种促进肿瘤生长和进展的过程。

目的

本研究旨在评估ASA对皮肤黑色素瘤(CM)和葡萄膜黑色素瘤(UM)的影响。

方法

用5 mM ASA处理人CM和UM细胞,并评估细胞功能的变化。使用基于ELISA的检测方法测定10种促血管生成细胞因子,以确定ASA的抗血管生成作用,然后通过蛋白质印迹法进行验证。最后,对经ASA处理的细胞进行蛋白质组学分析,以阐明可能导致ASA对黑色素瘤细胞产生作用的变化。

结果

ASA处理显著抑制了CM和UM的增殖、侵袭和迁移能力,并导致血管生成素和胎盘生长因子(PIGF)分泌显著减少。质谱分析显示,CM和UM细胞系中有179种与ASA相关的蛋白质变化。

结论

这些结果表明,ASA可能作为转移性CM和UM的辅助治疗有效。未来需要进行研究以确定负责ASA抗肿瘤作用的调控靶点。

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