Unknown

Dataset Information

0

Progressive resistance of BTK-143 osteosarcoma cells to Apo2L/TRAIL-induced apoptosis is mediated by acquisition of DcR2/TRAIL-R4 expression: resensitisation with chemotherapy.


ABSTRACT: Apo2 ligand (Apo2L, also known as TRAIL) is a member of the tumour necrosis factor (TNF) family of cytokines that selectively induces the death of cancer cells, but not of normal cells. We observed that recombinant Apo2L/TRAIL was proapoptotic in early-passage BTK-143 osteogenic sarcoma cells, inducing 80% cell death during a 24 h treatment period. Apo2L/TRAIL-induced apoptosis was blocked by caspase inhibition. With increasing passage in culture, BTK-143 cells became progressively resistant to the apoptotic effects of Apo2L/TRAIL. RNA and flow cytometric analysis demonstrated that resistance to Apo2L/TRAIL was paralleled by progressive acquisition of the decoy receptor, DcR2. Blocking of DcR2 function with a specific anti-DcR2 antibody restored sensitivity to Apo2L/TRAIL in a dose-dependent manner. Importantly, treatment of resistant cells with the chemotherapeutic agents doxorubicin, cisplatin and etoposide reversed the resistance to Apo2L/TRAIL, which was associated with drug-induced upregulation of mRNA encoding the death receptors DR4 and DR5. BTK-143 cells thus represent a useful model system to investigate both the mechanisms of acquisition of resistance of tumour cells to Apo2L/TRAIL and the use of conventional drugs and novel agents to overcome resistance to Apo2L/TRAIL.

SUBMITTER: Bouralexis S 

PROVIDER: S-EPMC2394221 | BioStudies | 2003-01-01

SECONDARY ACCESSION(S): 10.1038/sj.bjc.6601021

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC3784419 | BioStudies
2013-01-01 | S-EPMC3576345 | BioStudies
2005-01-01 | S-EPMC1134734 | BioStudies
2008-01-01 | S-EPMC2562222 | BioStudies
2011-01-01 | S-EPMC5568243 | BioStudies
2007-08-31 | GSE8332 | GEO
2014-01-01 | S-EPMC4040674 | BioStudies
1000-01-01 | S-EPMC4624014 | BioStudies
2015-01-01 | S-EPMC4240732 | BioStudies
2018-01-01 | S-EPMC6014359 | BioStudies