Drug resistance does not correlate with resistance to Fas-mediated apoptosis

Abstract

Recent reports have correlated multidrug resistance (MDR) and P-glycoprotein expression with decreased Fas expression and resistance to Fas-mediated apoptosis. We report the MRP-overexpressing MDR subline CEM/E1000 has the same Fas expression (MFI 74.3 +/- 0.7) as the parental CCRF-CEM T-cell leukaemia cells (MFI 70.0 +/- 3.6; P>0.05), and that the level of apoptosis induced by anti-Fas antibody or drug was similar in both cell lines. Further the P-glycoprotein-expressing CEM/VLB(100) subline of the CCRF-CEM cells showed increased Fas expression (MFI 114.8 +/- 3.6; P<0.001) and no resistance to Fas-mediated apoptosis. This questions the hypothesis that selection of drug resistance results in resistance to Fas-mediated apoptosis, with important implications for the rational use of immunotherapy in the treatment of drug resistant cancer.