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Research Paper|Volume 15, Issue 24|pp 15183—15195

Inhibition of TGF-β1-induced epithelial-mesenchymal transition in gliomas by DMC-HA

Lei Shi1, Zhimin Wang2, Jun Rong3, Xifeng Fei4, Xuetao Li2, Bao He1, Weiyi Gong1, Jin Qian3
  • 1Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Suzhou 215300, P.R. China
  • 2Department of Neurosurgery, Dushu Lake Hospital Affiliated to Soochow University, Suzhou 215300, P.R. China
  • 3Department of Neurosurgery, Xuancheng People’s Hospital, The Affiliated Xuancheng Hospital of Wannan Medical College, Anhui 242099, P.R. China
  • 4Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou 215028, P.R. China
* Equal contribution
Received: September 4, 2023Accepted: November 13, 2023Published: December 27, 2023
https://doi.org/10.18632/aging.205340

Copyright: © 2023 Shi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

DMC-HA, a novel HDAC inhibitor, has previously demonstrated antiproliferative activity against various cancers, including gliomas. However, the role of DMC-HA in the regulation of EMT and its underlying mechanisms remain unknown. This study aimed to explore the effects of DMC-HA on TGF-β1-induced EMT in human gliomas and the underlying mechanisms involved. Our results showed that TGF-β1 induced EMT of U87 and U251 cells, leading to a decrease in epithelial marker ZO-1 and an increase in mesenchymal markers N-cadherin and Vimentin. Moreover, TGF-β1 treatment resulted in a significant increase in the migratory and invasive abilities of the cells. However, treatment with DMC-HA effectively inhibited the augmented migration and invasion of glioma cells induced by TGF-β1. Additionally, DMC-HA inhibits TGF-β1-induced EMT by suppressing canonical Smad pathway and non-canonical TGF-β/Akt and Erk signalling pathways. These findings suggest that DMC-HA has potential therapeutic implications for gliomas by inhibiting EMT progression.