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Study on the Effect of EZH2 Inhibitor Combined with TIGIT Monoclonal Antibody against Multiple Myeloma Cells

EZH2, a member of the polycomb repressive complex 2, induces trimethylation of the downstream gene at the histone three lysine 27 (H3K27me3) position to inhibit tumor cell proliferation. Here, we showed that the apoptosis rate and apoptotic protein expression increased after EZH2 inhibition, whereas...

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Autores principales: Liu, Zhaoyun, Jia, Yue, Yang, Chun, Liu, Hui, Shen, Hongli, Wang, Hao, Fu, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218613/
https://www.ncbi.nlm.nih.gov/pubmed/37239949
http://dx.doi.org/10.3390/ijms24108603
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author Liu, Zhaoyun
Jia, Yue
Yang, Chun
Liu, Hui
Shen, Hongli
Wang, Hao
Fu, Rong
author_facet Liu, Zhaoyun
Jia, Yue
Yang, Chun
Liu, Hui
Shen, Hongli
Wang, Hao
Fu, Rong
author_sort Liu, Zhaoyun
collection PubMed
description EZH2, a member of the polycomb repressive complex 2, induces trimethylation of the downstream gene at the histone three lysine 27 (H3K27me3) position to inhibit tumor cell proliferation. Here, we showed that the apoptosis rate and apoptotic protein expression increased after EZH2 inhibition, whereas key molecules of the NF-κB signaling pathway and the downstream target genes were inhibited. Additionally, the expression of CD155, a TIGIT high-affinity ligand in multiple myeloma (MM) cells, was decreased by the mTOR signaling pathway. Furthermore, the combination of EZH2 inhibitor and TIGIT monoclonal antibody blockade enhanced the anti-tumor effect of natural killer cells. In summary, the EZH2 inhibitor not only plays an anti-tumor role as an epigenetic drug, but also enhances the anti-tumor effect of the TIGIT monoclonal antibody by affecting the TIGIT-CD155 axis between NK cells and MM cells, thus providing new ideas and theoretical basis for the treatment of MM patients.
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spelling pubmed-102186132023-05-27 Study on the Effect of EZH2 Inhibitor Combined with TIGIT Monoclonal Antibody against Multiple Myeloma Cells Liu, Zhaoyun Jia, Yue Yang, Chun Liu, Hui Shen, Hongli Wang, Hao Fu, Rong Int J Mol Sci Article EZH2, a member of the polycomb repressive complex 2, induces trimethylation of the downstream gene at the histone three lysine 27 (H3K27me3) position to inhibit tumor cell proliferation. Here, we showed that the apoptosis rate and apoptotic protein expression increased after EZH2 inhibition, whereas key molecules of the NF-κB signaling pathway and the downstream target genes were inhibited. Additionally, the expression of CD155, a TIGIT high-affinity ligand in multiple myeloma (MM) cells, was decreased by the mTOR signaling pathway. Furthermore, the combination of EZH2 inhibitor and TIGIT monoclonal antibody blockade enhanced the anti-tumor effect of natural killer cells. In summary, the EZH2 inhibitor not only plays an anti-tumor role as an epigenetic drug, but also enhances the anti-tumor effect of the TIGIT monoclonal antibody by affecting the TIGIT-CD155 axis between NK cells and MM cells, thus providing new ideas and theoretical basis for the treatment of MM patients. MDPI 2023-05-11 /pmc/articles/PMC10218613/ /pubmed/37239949 http://dx.doi.org/10.3390/ijms24108603 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Zhaoyun
Jia, Yue
Yang, Chun
Liu, Hui
Shen, Hongli
Wang, Hao
Fu, Rong
Study on the Effect of EZH2 Inhibitor Combined with TIGIT Monoclonal Antibody against Multiple Myeloma Cells
title Study on the Effect of EZH2 Inhibitor Combined with TIGIT Monoclonal Antibody against Multiple Myeloma Cells
title_full Study on the Effect of EZH2 Inhibitor Combined with TIGIT Monoclonal Antibody against Multiple Myeloma Cells
title_fullStr Study on the Effect of EZH2 Inhibitor Combined with TIGIT Monoclonal Antibody against Multiple Myeloma Cells
title_full_unstemmed Study on the Effect of EZH2 Inhibitor Combined with TIGIT Monoclonal Antibody against Multiple Myeloma Cells
title_short Study on the Effect of EZH2 Inhibitor Combined with TIGIT Monoclonal Antibody against Multiple Myeloma Cells
title_sort study on the effect of ezh2 inhibitor combined with tigit monoclonal antibody against multiple myeloma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218613/
https://www.ncbi.nlm.nih.gov/pubmed/37239949
http://dx.doi.org/10.3390/ijms24108603
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