Resistance to gemcitabine in a lymphoma cell line resistant to Fas-mediated apoptosis.
Anticancer Res
; 24(2B): 851-7, 2004.
Article
in En
| MEDLINE
| ID: mdl-15161037
ABSTRACT
BACKGROUND:
The T-cell lymphoma cell line HuT78B1, selected for resistance to Fas-mediated apoptosis, resulted unexpectedly resistant to the apoptotic and cytotoxic effects of gemcitabine (dFdC). We investigated whether this resistance was due to the impairment of the Fas/Fas-ligand (FasL) system. MATERIALS ANDMETHODS:
dFdC effects were studied in HuT78B1 and in the parental Fas-sensitive HuT78 cells exposed to inhibitors of the Fas/FasL system.RESULTS:
FasL- and Fas-blocking antibodies did not interfere with dFdC-induced apoptosis in HuT78 cells, whereas inhibitors of caspase-8, -9, -1 or -3 had partial inhibitory effects. Notably, in HuT78B1 cells there was a markedly reduced dFdC accumulation notwithstanding a high activity of the activating enzyme deoxycytidine kinase. dFdC accumulation in HuT78 cells was unaffected by a Fas-blocking antibody.CONCLUSION:
This is the first time that the selection of a Fas-resistant cell line led to the isolation of a cell clone unable to accumulate the deoxycytidine analog dFdC. Our results show that this alteration is independent from the impairment of the Fas/FasL system.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Membrane Glycoproteins
/
Lymphoma, T-Cell
/
Apoptosis
/
Fas Receptor
/
Deoxycytidine
/
Antimetabolites, Antineoplastic
Limits:
Humans
Language:
En
Journal:
Anticancer Res
Year:
2004
Document type:
Article
Affiliation country:
Italy