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海参素 A 通过 Akt/JNK 和 P38 MAPK 信号通路抑制转移前列腺癌中 RUNX1 增强的 EMT。

Holothurin A Inhibits RUNX1-Enhanced EMT in Metastasis Prostate Cancer via the Akt/JNK and P38 MAPK Signaling Pathway.

机构信息

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

Chulabhorn International College of Medicine, Thammasat University, Pathumthani 12120, Thailand.

出版信息

Mar Drugs. 2023 Jun 3;21(6):345. doi: 10.3390/md21060345.

DOI:10.3390/md21060345
PMID:37367670
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10301049/
Abstract

Due to the challenge of prostate cancer (PCa) management, there has been a surge in efforts to identify more safe and effective compounds that can modulate the epithelial-mesenchymal transition (EMT) for driving metastasis. Holothurin A (HA), a triterpenoid saponin isolated from , has now been characterized for its diverse biological activities. However, the mechanisms of HA in EMT-driven metastasis of human PCa cell lines has not yet been investigated. Moreover, runt-related transcription factor 1 (RUNX1) acts as an oncogene in prostate cancer, but little is known about its role in the EMT. Thus, the purpose of this study was to determine how RUNX1 influences EMT-mediated metastasis, as well as the potential effect of HA on EMT-mediated metastasis in endogenous and exogenous RUNX1 expressions of PCa cell lines. The results demonstrated that RUNX1 overexpression could promote the EMT phenotype with increased EMT markers, consequently driving metastatic migration and invasion in PC3 cell line through the activation of Akt/MAPK signaling pathways. Intriguingly, HA treatment could antagonize the EMT program in endogenous and exogenous RUNX1-expressing PCa cell lines. A decreasing metastasis of both HA-treated cell lines was evidenced through a downregulation of MMP2 and MMP9 via the Akt/P38/JNK-MAPK signaling pathway. Overall, our approach first demonstrated that RUNX1 enhanced EMT-driven prostate cancer metastasis and that HA was capable of inhibiting the EMT and metastatic processes and should probably be considered as a candidate for metastasis PCa treatment.

摘要

由于前列腺癌 (PCa) 管理的挑战，人们一直在努力寻找更安全、更有效的化合物，以调节上皮-间充质转化 (EMT) 从而促进转移。从海参中分离出的三萜皂苷 Holothurin A (HA) 具有多种生物活性，现已得到鉴定。然而，HA 对人前列腺癌细胞系 EMT 驱动转移的机制尚未得到研究。此外， runt 相关转录因子 1 (RUNX1) 在前列腺癌中作为癌基因发挥作用，但对于其在 EMT 中的作用知之甚少。因此，本研究旨在确定 RUNX1 如何影响 EMT 介导的转移，以及 HA 对前列腺癌细胞系中内源性和外源性 RUNX1 表达的 EMT 介导的转移的潜在影响。结果表明，RUNX1 的过表达可以促进 EMT 表型，增加 EMT 标志物，从而通过激活 Akt/MAPK 信号通路促进 PC3 细胞系的转移性迁移和侵袭。有趣的是，HA 处理可以拮抗内源性和外源性 RUNX1 表达的 PCa 细胞系中的 EMT 程序。通过 Akt/P38/JNK-MAPK 信号通路下调 MMP2 和 MMP9，证实了 HA 处理的两种细胞系的转移减少。总的来说，我们的方法首次表明 RUNX1 增强了 EMT 驱动的前列腺癌转移，而 HA 能够抑制 EMT 和转移过程，因此可能被认为是治疗转移性前列腺癌的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df2d/10301049/d5ad84f66f59/marinedrugs-21-00345-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df2d/10301049/1d3a62e9a31a/marinedrugs-21-00345-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df2d/10301049/9ec24def903b/marinedrugs-21-00345-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df2d/10301049/05e980c75f47/marinedrugs-21-00345-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df2d/10301049/9911cadabccf/marinedrugs-21-00345-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df2d/10301049/e8e3972dc364/marinedrugs-21-00345-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df2d/10301049/b827714becb0/marinedrugs-21-00345-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df2d/10301049/d5ad84f66f59/marinedrugs-21-00345-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df2d/10301049/1d3a62e9a31a/marinedrugs-21-00345-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df2d/10301049/9ec24def903b/marinedrugs-21-00345-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df2d/10301049/05e980c75f47/marinedrugs-21-00345-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df2d/10301049/9911cadabccf/marinedrugs-21-00345-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df2d/10301049/e8e3972dc364/marinedrugs-21-00345-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df2d/10301049/b827714becb0/marinedrugs-21-00345-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df2d/10301049/d5ad84f66f59/marinedrugs-21-00345-g007.jpg

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