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.
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.
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.
In conclusion, we show that ABCB1 expression represents the primary (sometimes exclusive) resistance mechanism in neuroblastoma cells with acquired resistance to SNS-032.
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.
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.
Data from present study suggest that transcriptional inactivation of MDR1 gene due to increased MDR1 promoter methylation may be a contributing factor in pathogenesis and progression of neuroblastoma tumors, and may be used in designing an effective treatment therapy to neuroblastoma patients.
Multidrug resistance protein 1 has been previously implicated in the development of drug resistance, particularly with regard to influencing clinical outcomes in neuroblastoma.
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.
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.
Expression of N-myc, c-myc, and MDR-1 proteins in newly established neuroblastoma cell lines: a study by immunofluorescence staining and flow cytometry.
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.
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.
To rule out the possibility that multidrug resistance (MDR) genes are involved in development of acquired drug resistance in murine neuroblastoma (rMNB/MDL) cells made resistant to MDL, the expression of Mdr1a, Mdr1b, Mdr2 (multidrug resistance/P-glycoprotein), and Mrp-1 (multidrug resistance associated protein) was examined in rMNB-MDL cells.
Drug exposure time studies were used to determine that topotecan (Hycamtin) exhibited great cytotoxic activity against SK-N-SH, IMR-32 and LAN-1 neuroblastoma human cell lines.
Here, we demonstrate that the ABC domain of the RARbeta(2) protein alone was sufficient for the growth inhibitory effects of RARbeta(2) on neuroblastoma cells.
Moreover, using the same experimental model, conditioned media obtained from 5 different human NB cell lines MYCN-amplified (HTLA-230, LAN-5 and GI-LI-N) or nonamplified (ACN and SH-SY5Y) and biopsy fragments obtained from xenografts derived from 4 NB cell lines (HTLA-230, GI-LI-N, ACN and SH-SY5Y) injected in nude mice were assayed for angiogenic potential.
In conclusion, expression of HLA-ABC and several co-regulated CAMs was shown to be associated with a differentiated phenotype in NB, with an overall decreased sensitivity to NK/LAK effector cells.
A ChIP assay demonstrated that E2F1 binds directly to the miR‑202 promoter region. miR‑202 is activated by E2F1 and in turn downregulates MYCN protein expression in the neuroblastoma cell line LAN‑5.