Chin-Yee I, Alshammari S, Anderson L, Kadri M, Keeney M
Flow Cytometry Unit, London Health Sciences Centre, University of Western Ontario, Canada.
Clin Lab Haematol. 1996 Jun;18(2):99-104. doi: 10.1046/j.1365-2257.1996.00146.x.
P-glycoprotein (Pgp) is a transmembrane protein associated with multiple drug resistance. Pgp can be detected by several monoclonal antibodies or its activity inferred by measuring drug uptake. We compared two methods for quantitating Pgp in 32 patients with chronic lymphocytic leukaemia. The monoclonal antibody 4E3, which recognizes an external epitope of Pgp, was detected by flow cytometry. Intracellular daunorubicin (DNR) accumulation was measured by flow cytometry in the presence (treated) and absence (control) of cyclosporin, an agent known to inhibit Pgp. Correlation between the degree of positivity on the drug uptake assay and Pgp detected by monoclonal antibody 4E3 was poor (r = 0.06). No association with previous drug exposure or lymphocyte doubling time and Pgp positivity was found in this series of patients. Poor correlation between assays might reflect a lack of sensitivity of the DNR uptake assay. Drug accumulation may be influenced by other cellular efflux pumps unrelated to Pgp, making the DNR assay non-specific.
P-糖蛋白（Pgp）是一种与多药耐药相关的跨膜蛋白。Pgp可通过几种单克隆抗体进行检测，或通过测量药物摄取来推断其活性。我们比较了两种定量32例慢性淋巴细胞白血病患者Pgp的方法。通过流式细胞术检测识别Pgp外部表位的单克隆抗体4E3。在存在（处理组）和不存在（对照组）已知可抑制Pgp的环孢素的情况下，通过流式细胞术测量细胞内柔红霉素（DNR）的蓄积。药物摄取试验的阳性程度与单克隆抗体4E3检测到的Pgp之间的相关性较差（r = 0.06）。在这一系列患者中，未发现与既往药物暴露或淋巴细胞倍增时间及Pgp阳性之间存在关联。试验之间的相关性较差可能反映了DNR摄取试验缺乏敏感性。药物蓄积可能受与Pgp无关的其他细胞外排泵的影响，使得DNR试验具有非特异性。
