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胡芦巴碱通过降低 MMP 活性和下调 N-钙黏蛋白和纤连蛋白来抑制黑色素瘤细胞迁移和侵袭。

Galbanic acid suppresses melanoma cell migration and invasion by reducing MMP activity and downregulating N-cadherin and fibronectin.

机构信息

Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Stem Cell and Regenerative Medicine Research Group, Academic Center for Education, Culture and Research (ACECR)-Khorasan Razavi, Mashhad, Iran.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2024 Aug;397(8):5779-5788. doi: 10.1007/s00210-024-02981-4. Epub 2024 Feb 7.


DOI:10.1007/s00210-024-02981-4
PMID:38324091
Abstract

High mortality rate of melanoma is due to the metastasis of malignant cells. Galbanic acid (GBA) is a natural sesquiterpene coumarin with valuable pharmaceutical activities. Our study aimed to investigate whether GBA can affect the migration, invasion, and adhesion of melanoma cells. The survival rate of B16F10 cells was measured using the alamarBlue assay. Scratch, adhesion, and invasion assays were performed to determine the effect of GBA on metastatic behavior of cells. Moreover, gelatin zymography was done to assess the activity of MMP-2 and MMP-9, and qRT-PCR was used to investigate the effect of GBA on the expression of candidate genes. Based on the results of alamarBlue assay, 40 µM GBA was chosen as the optimum concentration for all tests. Our findings indicated that GBA significantly decreased the invasion and migration of B16F10 cells while enhancing their adhesion ability. In addition, gelatin zymography demonstrated that GBA reduced the enzymatic activity of MMP-2 and MMP-9. Moreover, qRT-PCR revealed that GBA reduced the expression of N-cadherin and fibronectin. Current findings demonstrated, for the first time, that GBA inhibited the migration and invasion of melanoma cells via reducing the activity of MMP-2 and MMP-9 and downregulating N-cadherin and fibronectin expression. Accordingly, GBA could be suggested as a potential therapeutic agent for the treatment of melanoma.

摘要

黑色素瘤的高死亡率归因于恶性细胞的转移。蛇床子素(GBA)是一种具有重要药用价值的天然倍半萜香豆素。我们的研究旨在探讨 GBA 是否能影响黑色素瘤细胞的迁移、侵袭和黏附。使用 alamarBlue 法测定 B16F10 细胞的存活率。通过划痕、黏附和侵袭实验来确定 GBA 对细胞转移行为的影响。此外,通过明胶酶谱法评估 MMP-2 和 MMP-9 的活性,并用 qRT-PCR 检测 GBA 对候选基因表达的影响。根据 alamarBlue 实验的结果,选择 40 µM 的 GBA 作为所有实验的最佳浓度。我们的研究结果表明,GBA 显著降低了 B16F10 细胞的侵袭和迁移能力,同时增强了它们的黏附能力。此外,明胶酶谱法表明 GBA 降低了 MMP-2 和 MMP-9 的酶活性。此外,qRT-PCR 显示 GBA 降低了 N-钙黏蛋白和纤连蛋白的表达。目前的研究结果首次表明,GBA 通过降低 MMP-2 和 MMP-9 的活性以及下调 N-钙黏蛋白和纤连蛋白的表达来抑制黑色素瘤细胞的迁移和侵袭。因此,GBA 可被建议作为治疗黑色素瘤的潜在治疗剂。

相似文献

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Galbanic acid suppresses melanoma cell migration and invasion by reducing MMP activity and downregulating N-cadherin and fibronectin.

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[6]
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引用本文的文献

[1]
Extracellular matrix dynamics in tumor immunoregulation: from tumor microenvironment to immunotherapy.

J Hematol Oncol. 2025-6-19

[2]
Harnessing the metastatic potential of human osteosarcoma cells by natural coumarin galbanic acid.

Naunyn Schmiedebergs Arch Pharmacol. 2025-4-7

[3]
Alarmins in cutaneous malignant melanoma: An updated overview of emerging evidence on their pathogenetic, diagnostic, prognostic, and therapeutic role.

J Dermatol. 2024-7

本文引用的文献

[1]
Management of Advanced Invasive Melanoma: New Strategies.

Adv Ther. 2023-8

[2]
The journey from melanocytes to melanoma.

Nat Rev Cancer. 2023-6

[3]
European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics: Update 2022.

Eur J Cancer. 2022-7

[4]
The extracellular matrix proteins type I collagen, type III collagen, fibronectin, and laminin 421 stimulate migration of cancer cells.

FASEB J. 2021-7

[5]
Recent Advances in the Treatment of Melanoma.

N Engl J Med. 2021-6-10

[6]
United States burden of melanoma and non-melanoma skin cancer from 1990 to 2019.

J Am Acad Dermatol. 2021-8

[7]
CDH2/N-cadherin and early diagnosis of invasion in patients with ductal carcinoma in situ.

Breast Cancer Res Treat. 2020-9

[8]
Cutaneous melanoma and the immunotherapy revolution (Review).

Int J Oncol. 2020-9

[9]
Effects of Galbanic Acid on Proliferation, Migration, and Apoptosis of Glioblastoma Cells Through the PI3K/Akt/MTOR Signaling Pathway.

Curr Mol Pharmacol. 2021

[10]
E-Cadherin in Pancreatic Ductal Adenocarcinoma: A Multifaceted Actor during EMT.

Cells. 2020-4-22

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