2. Academic Validation
  3. FK228 suppress the growth of human malignant pleural mesothelioma tumor independent to epithelioid or non-epithelioid histology

FK228 suppress the growth of human malignant pleural mesothelioma tumor independent to epithelioid or non-epithelioid histology

  • Mol Med. 2024 May 31;30(1):73. doi: 10.1186/s10020-024-00835-6.
James Mei-Lin Chan 1 2 3 4,  Yuan-Ching Chang 1 3 4,  Hua-Chen Chan 5 6,  Hsiu-Chuan Chan 7,  Wei-Chin Chang 8,  Liu-Fang Wang 4,  Tung-Hu Tsai 2,  Yu-Jen Chen 9 10 11 12,  Wen-Chien Huang 13 14 15
Affiliations

Affiliations

  • 1 Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
  • 2 Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • 3 Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
  • 4 Department of Medical Research, Mackay Memorial Hospital, New Taipei City, Taiwan.
  • 5 Department of Medical Laboratory Science, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
  • 6 Center for Lipid Biosciences, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
  • 7 PhD Program in Life Sciences, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 8 Pathology Department, Taipei Medical University Hospital, Taipei, Taiwan.
  • 9 Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. [email protected].
  • 10 Department of Medicine, Mackay Medical College, New Taipei City, Taiwan. [email protected].
  • 11 Department of Medical Research, Mackay Memorial Hospital, New Taipei City, Taiwan. [email protected].
  • 12 Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan. [email protected].
  • 13 Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan. [email protected].
  • 14 Department of Medicine, Mackay Medical College, New Taipei City, Taiwan. [email protected].
  • 15 Department of Medical Research, Mackay Memorial Hospital, New Taipei City, Taiwan. [email protected].
PMID: 38822233 DOI: 10.1186/s10020-024-00835-6
Abstract

Human malignant pleural mesothelioma (hMPM) is an aggressive, rare disease with a poor prognosis. Histologically, MPM is categorized into epithelioid, biphasic, and sarcomatoid subtypes, with the epithelioid subtype generally displaying a better response to treatment. Conversely, effective therapies for the non-epithelioid subtypes are limited. This study aimed to investigate the potential role of FK228, a histone deacetylase inhibitor, in the suppression of hMPM tumor growth. We conducted a comprehensive analysis of the histological and molecular characteristics of two MPM cell lines, CRL-5820 (epithelioid) and CRL-5946 (non-epithelioid). CRL-5946 cells and non-epithelioid patient-derived xenografted mice exhibited heightened growth rates compared to those with epithelioid MPM. Both CRL-5946 cells and non-epithelioid mice displayed a poor response to cisplatin. However, FK228 markedly inhibited the growth of both epithelioid and non-epithelioid tumor cells in vitro and in vivo. Cell cycle analysis revealed FK228-induced G1/S and mitotic arrest in MPM cells. Caspase Inhibitor experiments demonstrated that FK228-triggered Apoptosis occurred via a caspase-dependent pathway in CRL-5946 but not in CRL-5820 cells. Additionally, a cytokine array analysis showed that FK228 reduced the release of growth factors, including platelet-derived and vascular endothelial growth factors, specifically in CRL-5946 cells. These results indicate that FK228 exhibits therapeutic potential in MPM by inducing cytotoxicity and modulating the tumor microenvironment, potentially benefiting both epithelioid and non-epithelioid subtypes.

Keywords

Epithelioid; Human malignant pleural mesothelioma (hMPM); Non-epithelioid; Romidepsin (FK228); Sarcomatoid.

Figures
Products