Multidrug resistance-associated protein gene expression and drug sensitivity in human lung cancer cells.
Multidrug resistance-associated protein (MRP) mRNA expression and drug sensitivity in lung cancer cells were examined, and the effects of verapamil, a modulating agent for MRP, on drug sensitivity were also tested. Nine cell lines expressed various levels of MRP gene expression but not the MDR1 gene. The levels were higher in non-small cell carcinoma cells (NSCLC) than in small cell carcinoma cells (SCLC). Clear correlations between the MRP gene level and the sensitivity to etoposide (VP-16) and doxorubicin (Dox) were observed except for one cell line which highly expressed DNA topoisomerase II. Positive correlations between the MRP gene levels in three cell lines and the modulation effects of verapamil in VP-16, Dox, and vincristine were observed. The present results indicate that MRP probably confers intrinsic multidrug resistance in NSCLC rather than in SCLC.
Narasaki
F
F
Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Oka
M
M
Fukuda
M
M
Ikeda
K
K
Terashi
K
K
Takatani
H
H
Nakamura
T
T
Soda
H
H
Kohno
S
S
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D005047:Etoposide / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D019450:Genes, MDR; D006801:Humans; D008175:Lung Neoplasms; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D002945:Cisplatin; D004317:Doxorubicin; D005047:Etoposide; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; D014700:Verapamil; D014750:Vincristine