耐药性与对Fas介导的细胞凋亡的抗性不相关。

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

作者信息

Cullen K V, Davey R A, Davey M W

机构信息

Department of Cell and Molecular Biology, University of Technology, Sydney, Westbourne Street, Gore Hill, Sydney, NSW 2065, Australia.

出版信息

Leuk Res. 2001 Jan;25(1):69-75. doi: 10.1016/s0145-2126(00)00085-0.

DOI:10.1016/s0145-2126(00)00085-0

PMID:11137563

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.

摘要

近期报告显示，多药耐药性（MDR）和P-糖蛋白表达与Fas表达降低及对Fas介导的凋亡产生抗性相关。我们报告称，过表达多药耐药相关蛋白（MRP）的MDR亚系CEM/E1000与亲代CCRF-CEM T细胞白血病细胞具有相同的Fas表达水平（平均荧光强度[MFI]为74.3±0.7）（MFI为70.0±3.6；P>0.05），并且抗Fas抗体或药物诱导的凋亡水平在这两种细胞系中相似。此外，CCRF-CEM细胞中表达P-糖蛋白的CEM/VLB(100)亚系显示Fas表达增加（MFI为114.8±3.6；P<0.001），且对Fas介导的凋亡无抗性。这对耐药性的选择会导致对Fas介导的凋亡产生抗性这一假说提出了质疑，这对于合理使用免疫疗法治疗耐药性癌症具有重要意义。