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Bortezomib and Arsenic Trioxide Activity on a Myelodysplastic Cell Line (P39): A Gene Expression Study.

Savlı H, Galimberti S, Sünnetçi D, Canesastraro M, Palumbo G, Nagy B, Di Raimondo F, Petrini M - Turk J Haematol (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

ABSTRACT

Introduction: We aimed to understand the molecular pathways affected by bortezomib and arsenic trioxide treatment on myelomonocytoid cell line P39.

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

Results: 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.

Discussion and conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Bortezomib and arsenic trioxide exert synergistic anti-proliferative and pro-apoptotic effects.
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f6: Bortezomib and arsenic trioxide exert synergistic anti-proliferative and pro-apoptotic effects.

Mentions: Bortezomib and ATO combination resulted in synergistic anti-proliferative and pro-apoptotic effects (Figure 6). PPAR, P53, IL6, IL2, hypoxia, Huntington’s disease, TLR and cell cycle were the pathways more significantly modified in the the IPA analysis of our data, when P39 was co-incubated with bortezomib/ATO. Moreover, we observed SHC1, MLL, ITGAV, BCRA2, HMOX1, ICAM1, JUN, PMAP1 and beta estradiol genes were down-regulated whereas BRCA2, FOXA1, LY96 and AKR1C1 genes were up-regulated. Levels and inter relationships were defined in Figure 7.


Bortezomib and Arsenic Trioxide Activity on a Myelodysplastic Cell Line (P39): A Gene Expression Study.

Savlı H, Galimberti S, Sünnetçi D, Canesastraro M, Palumbo G, Nagy B, Di Raimondo F, Petrini M - Turk J Haematol (2015)

Bortezomib and arsenic trioxide exert synergistic anti-proliferative and pro-apoptotic effects.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4563195&req=5

f6: Bortezomib and arsenic trioxide exert synergistic anti-proliferative and pro-apoptotic effects.
Mentions: Bortezomib and ATO combination resulted in synergistic anti-proliferative and pro-apoptotic effects (Figure 6). PPAR, P53, IL6, IL2, hypoxia, Huntington’s disease, TLR and cell cycle were the pathways more significantly modified in the the IPA analysis of our data, when P39 was co-incubated with bortezomib/ATO. Moreover, we observed SHC1, MLL, ITGAV, BCRA2, HMOX1, ICAM1, JUN, PMAP1 and beta estradiol genes were down-regulated whereas BRCA2, FOXA1, LY96 and AKR1C1 genes were up-regulated. Levels and inter relationships were defined in Figure 7.

Bottom Line: 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.

View Article: PubMed Central - PubMed

ABSTRACT

Introduction: We aimed to understand the molecular pathways affected by bortezomib and arsenic trioxide treatment on myelomonocytoid cell line P39.

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

Results: 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.

Discussion and conclusion: 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.

No MeSH data available.


Related in: MedlinePlus