Bortezomib and Arsenic Trioxide Activity on a Myelodysplastic Cell Line (P39): A Gene Expression Study.
We aimed to understand the molecular pathways affected by bortezomib and arsenic trioxide treatment on myelomonocytoid cell line P39.



Oligonucleotide microarray platforms were used for gene expression and pathway analysis. Confirmation studies were performed using quantitative real time PCR.



Bortezomib treatment has shown upregulated DIABLO and NF-κBIB (a NF-κB inhibitor) and downregulated NF-κB1, NF-κB2, and BIRC1 gene expressions. Combination treatment of the two compounds showed gene expression deregulations in concordance by the results of single bortezomib treatment. Especially, P53 was a pathway more significantly modified and a gene network centralized around the beta estradiol gene. Beta estradiol, BRCA2, and FOXA1 genes were remarkable deregulations in our findings.



Results support the suggestions about possible use of proteasome inhibitors in the treatment of high-risk myelodysplastic syndrome (MDS). NF-κB was observed as an important modulator in leukemic transformation of MDS.
Hakan
H
Savlı
Sara
S
Galimberti
Deniz
D
Sünnetçi
Martina
M
Canesastraro
Giuseppe
G
Palumbo
Balint
B
Nagy
Francesco
F
Di Raimondo
Mario
M
Petrini
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D000069286:Bortezomib / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D018450:Disease Progression; D004357:Drug Synergism; D004958:Estradiol / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D015477:Leukemia, Myelomonocytic, Chronic / Q000473:pathology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D010087:Oxides / Q000494:pharmacology*; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D001152:Arsenicals; D016328:NF-kappa B; D009363:Neoplasm Proteins; D010087:Oxides; D061988:Proteasome Inhibitors; D004958:Estradiol; D000069286:Bortezomib; D000077237:Arsenic Trioxide