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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-10218613 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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