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 cel l viability and proliferation we examine the cytotoxic effect of lovas tatin on a drug sensitive myeloma cell line (RPMI 8226) and a multidru g resistant (MDR) clone (8226/Dox40), that was approximately 100-fold less sensitive to doxorubicin. The RPMI 8226 cells were sensitive to l ovastatin with an IC50 of 15.8 mu g/ml. However, the MDR subline exhib ited a collateral sensitivity to lovastatin, with an IC50 of 1.7 mu M, thus having a 9.3-fold greater sensitivity to lovastatin than the par ental 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 M DR cells 8226/Dox40 might be part of a more general phenomenon that me rits further investigation.