Effects of lovastatin on a human myeloma cell line: increased sensitivity of a multidrug-resistant subline that expresses the 170 kDa P-glycoprotein.
Using a fluorometric microculture cytotoxicity assay for measuring cell viability and proliferation we examine the cytotoxic effect of lovastatin on a drug sensitive myeloma cell line (RPMI 8226) and a multidrug resistant (MDR) clone (8226/Dox40), that was approximately 100-fold less sensitive to doxorubicin. The RPMI 8226 cells were sensitive to lovastatin with an IC50 of 15.8 micrograms/ml. However, the MDR subline exhibited a collateral sensitivity to lovastatin, with an IC50 of 1.7 microM, thus having a 9.3-fold greater sensitivity to lovastatin than the parental cell line. The combination of doxorubicin and lovastatin did not show any synergistic or antagonistic effects on any of the cell lines. The increased sensitivity to lovastatin of the P-gp 170-expressing MDR cells 8226/Dox40 might be part of a more general phenomenon that merits further investigation.
Holmberg
M
M
Department of Infectious Diseases, University Hospital, Uppsala University, Sweden.
Sandberg
C
C
Nygren
P
P
Larsson
R
R
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D002455:Cell Division / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D005434:Flow Cytometry; D006801:Humans; D007202:Indicators and Reagents; D008148:Lovastatin / Q000494:pharmacology*; D009101:Multiple Myeloma / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007202:Indicators and Reagents; D004317:Doxorubicin; D008148:Lovastatin