PMID- 35873012
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220726
IS  - 1726-6890 (Electronic)
IS  - 1735-0328 (Print)
IS  - 1726-6882 (Linking)
VI  - 21
IP  - 1
DP  - 2022 Dec
TI  - Expression Modulation of Immune Checkpoint Molecules by Ibrutinib and Everolimus 
      Through STAT3 in MCF-7 Breast Cancer Cells.
PG  - e127352
LID - 10.5812/ijpr-127352 [doi]
LID - e127352
AB  - 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.
CI  - Copyright (c) 2022, Author(s).
FAU - Soltanshahi, Mohsen
AU  - Soltanshahi M
AD  - Department of Immunology, School of Medicine, Mazandaran University of Medical 
      Sciences, Sari, Iran.
AD  - Student Research Committee, Mazandaran University of Medical Sciences, Sari, 
      Iran.
FAU - Taghiloo, Saeid
AU  - Taghiloo S
AD  - Department of Immunology, School of Medicine, Mazandaran University of Medical 
      Sciences, Sari, Iran.
AD  - Student Research Committee, Mazandaran University of Medical Sciences, Sari, 
      Iran.
FAU - Asgarian-Omran, Hossein
AU  - Asgarian-Omran H
AD  - Gastrointestinal Cancer Research Center, Noncommunicable Diseases Institute, 
      Mazandaran University of Medical Sciences, Sari, Iran.
AD  - Department of Immunology, School of Medicine, Mazandaran University of Medical 
      Sciences, Sari, Iran.
LA  - eng
PT  - Journal Article
DEP - 20220521
PL  - Netherlands
TA  - Iran J Pharm Res
JT  - Iranian journal of pharmaceutical research : IJPR
JID - 101208407
PMC - PMC9293249
OTO - NOTNLM
OT  - Breast Cancer
OT  - CD155
OT  - Galectin-9
OT  - PD-L1
OT  - STAT3
OT  - Small-Molecule Inhibitors
COIS- Conflict of Interests: The authors state that they conducted the research 
      independently of any commercial or financial relationships. The authors declare 
      that none of them listed on the manuscript work for a government agency whose 
      primary mission is not research or education.
EDAT- 2022/07/26 06:00
MHDA- 2022/07/26 06:01
PMCR- 2022/05/21
CRDT- 2022/07/25 03:28
PHST- 2021/12/30 00:00 [received]
PHST- 2022/04/08 00:00 [revised]
PHST- 2022/04/26 00:00 [accepted]
PHST- 2022/07/25 03:28 [entrez]
PHST- 2022/07/26 06:00 [pubmed]
PHST- 2022/07/26 06:01 [medline]
PHST- 2022/05/21 00:00 [pmc-release]
AID - 10.5812/ijpr-127352 [doi]
PST - epublish
SO  - Iran J Pharm Res. 2022 May 21;21(1):e127352. doi: 10.5812/ijpr-127352. 
      eCollection 2022 Dec.