Expression of N-myc, c-myc, and MDR-1 proteins in newly established neuroblastoma cell lines: a study by immunofluorescence staining and flow cytometry.
We conclude that most neuroblastoma cell lines are sensitive to YM155 in the low nM range and that resistant cells can be sensitised by ABCB1 inhibitors.
Lovastatin, a nonreversible inhibitor of HMG-CoA reductase, induced extensive cytotoxicity that was restricted to drug-resistant P-glycoprotein-expressing neuroblastoma cell lines.
MDR1 RNA levels were occasionally elevated in other untreated cancers, including neuroblastoma, acute lymphocytic leukemia (ALL) in adults, acute nonlymphocytic leukemia (ANLL) in adults, and indolent non-Hodgkin's lymphoma.
A similar strong association has been observed between the expression of P-glycoprotein and outcome of treatment in certain malignancies in children, such as neuroblastoma, rhabdomyosarcoma, and acute lymphoblastic leukemia.
Decreased expression of the N-myc oncogene in neuroblastoma cell lines SH-SY5Y and BE(2)-C, following treatment with retinoic acid, was paralleled by down-regulation of MRP gene expression, contrasting with increased expression of the MDR1 gene.
Though Pgp expression is detectable and functional in neuroblastoma cells, but its presence does not provide much information to the complex phenomenon of chemotherapy resistance in patients.
Mechanistically, the synergy was based on a lapatinib induced inhibition of the multidrug-resistance efflux transporter ABCB1, which is frequently expressed in resistant neuroblastoma cells, which allowed prolonged and elevated cytotoxicity of YM155.In addition, the drug combination (i.e. lapatinib plus YM155) decreased neuroblastoma tumor size in an in vivo model.
Hypermethylation of the miR-137 promoter and negative regulation of miR-137 by CAR contribute in part to reduced miR-137 expression and increased CAR and MDR1 expression in doxorubicin-resistant neuroblastoma cells.
Here, we demonstrate upregulation of multidrug transporters ABCB1 and ABCG2 as a major mode of resistance to THZ1, a covalent inhibitor of CDKs 7, 12, and 13 in neuroblastoma and lung cancer.
This study offers compelling evidence that (a) IGR-N-91 is a human neuroblastoma xenograft model able to induce metastasis in nude mice, (b) an increase in MYCN and MDR1 transcripts levels is associated with the metastatic process, and (c) IGR-N-91 provides a biological tool for the study of gene activations during tumor dissemination in neuroblastoma.
Many of the neuroblastoma samples were also evaluated for N-myc amplification but there was no correlation between N-myc copy number and the level of MDR1 mRNA expression.
Multidrug resistance protein 1 has been previously implicated in the development of drug resistance, particularly with regard to influencing clinical outcomes in neuroblastoma.
Because expression of mdr-1 is increased in neuroblastoma cell lines by differentiating agents, the authors hypothesized a similar correlation with differentiation in vivo in neuroblastomas.
The results indicate that the level of MDR1 mRNA expression is associated with previous chemotherapy, including drugs that select the multidrug resistance phenotype in vitro regardless of neuroblastoma tissue origin or N-myc content in the genome.
A panel of monoclonal antibodies (MAbs) to P-glycoprotein was developed by immunization of mice with multidrug-resistant human neuroepithelioma and neuroblastoma cells.
Sections from formalin-fixed paraffin-embedded tumor blocks from 52 neuroblastoma cases (17 with localized, 35 with advanced disease) were subjected to immunohistochemistry for P-gp and GST-pi expressions.
To this end, we used an inducible siRNA (small interfering RNA) expression system to silence the expression of MRP1 and MDR1 in human neuroblastoma SH-SY5Y cells.
Here, we present the effect of the N-(2-hydroxypropyl) methacrylamide-based polymer conjugate with P-gp inhibitor ritonavir (RIT) on the increase of free doxorubicin (DOX) and polymer-bound DOX cytotoxicity in the human neuroblastoma 4 cell line and its resistant clones to different cytostatics.
Combination therapy showed a synergistic activity between doxorubicin and either bioconjugate or nanocarrier on BE(2)C. More interestingly, on BE(2)C/ADR we recorded both the reversion of doxorubicin resistance mechanism as a consequence of decreased P-gp expression (Western Blot analysis) and a synergistic effect on cell viability, confirming the proposed nanohybrid as a very promising starting point for further research in neuroblastoma treatment.