An etoposide-resistant lung cancer subline overexpresses the multidrug resistance-associated protein.
Br J Cancer
; 72(3): 535-42, 1995 Sep.
Article
in En
| MEDLINE
| ID: mdl-7669558
ABSTRACT
We have characterised an etoposide-resistant subline of the small-cell lung cancer cell line, UMCC-1, derived at our centre. Subline UMCC-1/VP was developed by culturing the parent line in increasing concentrations of etoposide over 16 months. UMCC-1/VP is 20-fold resistant to etoposide by MTT assays, relative to the parent line, and is cross-resistant to doxorubicin, vincristine and actinomycin D, but not to taxol, cisplatin, melphalan, thiotepa or idarubicin. Topoisomerase II immunoblotting demonstrates a 50% reduction of the protein in the resistant subline. The UMCC-1/VP subline demonstrates a marked decrease in the accumulation of [3H]etoposide relative to the parent line, as well as a modest reduction in the accumulation of daunorubicin. Reverse transcription-polymerase chain reaction assays demonstrate no detectable mdr1 expression but marked expression of the multidrug resistance-associated protein (MRP) gene in the resistant subline. Northern blotting with an MRP cDNA probe confirms marked overexpression of the MRP gene only in the UMCC-1/VP subline. Western blotting with antisera against MRP peptide confirms a 195 kDa protein band in the UMCC-1/VP subline. Southern blotting experiments demonstrate a 10-fold amplification of the MRP gene in the resistant subline. Depletion of glutathione with buthionine sulphoximine sensitised UMCC-1/VP cells to daunorubicin and etoposide. Our studies indicate that MRP gene expression may be induced by etoposide and may lead to reduced accumulation of the drug.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tumor Cells, Cultured
/
Carcinoma, Small Cell
/
ATP-Binding Cassette Transporters
/
Etoposide
/
Lung Neoplasms
Type of study:
Risk_factors_studies
Limits:
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Br J Cancer
Year:
1995
Document type:
Article
Affiliation country: