Expression Modulation of Immune Checkpoint Molecules by Ibrutinib and Everolimus Through STAT3 in MCF-7 Breast Cancer Cells
| Author | Mohsen Soltanshahi | en |
| Author | Saeid Taghiloo | en |
| Author | Hossein Asgarian-Omran | en |
| Orcid | Mohsen Soltanshahi [0000-0003-1675-0765] | en |
| Orcid | Saeid Taghiloo [0000-0002-8813-6046] | en |
| Orcid | Hossein Asgarian-Omran [0000-0003-3816-8792] | en |
| Issued Date | 2022-12-31 | en |
| Abstract | Tumor-targeted therapy with small-molecule inhibitors (SMIs) has been demonstrated to be a highly effective therapeutic strategy for various cancers. However, their possible associations with immune evasion mechanisms remain unknown. This study examined the association of inhibitors of the protein kinase B (AKT), mammalian target of rapamycin (mTOR), and Bruton’s tyrosine kinase (BTK) signaling pathways with the expression of immune checkpoint ligands programmed death-ligand 1 (PD-L1), CD155, and galectin-9 (Gal-9) in a breast cancer cell line. MCF-7 cells were treated with everolimus, MK-2206, and ibrutinib. An MTT assay was used to determine the optimal dose for all drugs. A real-time polymerase chain reaction was utilized to measure the mRNA expression of PD-L1, CD155, and Gal-9. The western blot technique was also employed to evaluate the protein expression of the phosphorylated signal transducer and activator of transcription 3 (STAT3). The optimal doses of everolimus, MK-2206, and ibrutinib were observed to be 200, 320, and 2000 nM, respectively. The PD-L1 and CD155 mRNA expression was significantly decreased following the treatment with everolimus and ibrutinib, but not with MK-2206. There were no differences in Gal-9 expression between the single-treated and control groups; however, combined treatment with everolimus and ibrutinib increased its mRNA expression. Everolimus and ibrutinib both inhibited constitutive STAT3 phosphorylation in MCF-7, which was more pronounced in combination treatment. The findings regarding the modulation of PD-L1, CD155, and Gal-9 molecules by SMIs emphasize the crosstalk between the expression of these immune checkpoint molecules and AKT/mTOR/BTK signaling pathways through STAT3 as a critical transcription factor. | en |
| DOI | https://doi.org/10.5812/ijpr-127352 | en |
| Keyword | Breast Cancer | en |
| Keyword | Small-Molecule Inhibitors | en |
| Keyword | PD-L1 | en |
| Keyword | CD155 | en |
| Keyword | Galectin-9 | en |
| Keyword | STAT3 | en |
| Publisher | Brieflands | en |
| Title | Expression Modulation of Immune Checkpoint Molecules by Ibrutinib and Everolimus Through STAT3 in MCF-7 Breast Cancer Cells | en |
| Type | Research Article | en |