1. [Isoform Selectivity of HDAC Inhibitors Has a Significant Effect on PD-L1 Expression in the Triple-negative Cancer Cell Line MDA-MB-231].
- Author
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Nishino H, Hirata Y, Nagaoka Y, and Uesato S
- Subjects
- Cell Line, Histone Deacetylase Inhibitors pharmacology, Humans, Protein Isoforms therapeutic use, B7-H1 Antigen genetics, B7-H1 Antigen metabolism, Triple Negative Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms genetics, Triple Negative Breast Neoplasms metabolism
- Abstract
Various reports have been published in recent years on the effects of histone deacetylase (HDAC) inhibitors on programmed death ligand 1 (PD-L1) expression in cancer cells. The combination therapy of immune checkpoint inhibitors and HDAC inhibitors utilizing these effects has attracted attention as a new clinical treatment of triple-negative breast cancers. We investigated how the expression level of PD-L1 changes depending on the type of HDAC inhibitor exposed to triple-negative breast cancer cell line MDA-MB-231. We found that the mRNA expression level of PD-L1 was significantly decreased by Vorinostat and K-32 (pan-HDAC inhibitors) at high concentrations exhibiting low cell viability, while it was increased by high concentrations of K-560 (HDAC1,2 inhibitor) and Entinostat (HDAC1,3 inhibitor). On the other hand, the mRNA level of PD-L1 was increased by all of these HDAC inhibitors at low concentrations showing high cell viability. Of particular note, K-32 induced more PD-L1 mRNA than all the other HDAC inhibitors at the lowest concentration of 0.5 μM. This finding might suggest the usefulness of pan-HDAC inhibitors in clinical treatment in combination with immune checkpoint inhibitors.
- Published
- 2022
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