一种白三烯受体拮抗剂ONO - 1078可调节表达多药耐药蛋白的肺癌细胞的药物敏感性和白三烯C4外排。
A leukotriene receptor antagonist, ONO-1078, modulates drug sensitivity and leukotriene C4 efflux in lung cancer cells expressing multidrug resistance protein.
作者信息
Nakano R, Oka M, Nakamura T, Fukuda M, Kawabata S, Terashi K, Tsukamoto K, Noguchi Y, Soda H, Kohno S
机构信息
Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
出版信息
Biochem Biophys Res Commun. 1998 Oct 9;251(1):307-12. doi: 10.1006/bbrc.1998.9472.
ONO-1078 is a new class of peptide leukotriene receptor antagonist, and multidrug resistance protein (MRP) is a membrane tranporter of multiple anticancer drugs and endogenous leukotriene C4 (LTC4). We investigated the effects of ONO-1078 on drug sensitivity and LTC4-efflux in MRP-expressing lung cancer cells. Drug sensitivity, intracellular vincristine accumulation, and intracellular and extracellular LTC4 concentrations were measured with or without ONO-1078. The effect of ONO-1078 on MRP-mediated calcein-efflux was determined by flow cytometry. ONO-1078 (1 to 10 microM) dose-dependently enhanced the sensitivity of NCI-H520 cells to vincristine with the reduced accumulation, and also enhanced the sensitivity to doxorubicin and etoposide. ONO-1078 inhibited both LTC4- and calcein-efflux from the cells with increased intracellular accumulations. Our findings indicate that ONO-1078 modulates multidrug resistance and inhibits LTC4-efflux in lung cancer cells, by inhibition of MRP function.
ONO - 1078是一类新型的肽白三烯受体拮抗剂，多药耐药蛋白（MRP）是多种抗癌药物和内源性白三烯C4（LTC4）的膜转运蛋白。我们研究了ONO - 1078对表达MRP的肺癌细胞药物敏感性和LTC4外排的影响。在有或没有ONO - 1078的情况下，测量药物敏感性、细胞内长春新碱蓄积以及细胞内和细胞外LTC4浓度。通过流式细胞术确定ONO - 1078对MRP介导的钙黄绿素外排的影响。ONO - 1078（1至10微摩尔）以剂量依赖性方式增强NCI - H520细胞对长春新碱的敏感性，同时蓄积减少，并且还增强了对阿霉素和依托泊苷的敏感性。ONO - 1078抑制细胞的LTC4和钙黄绿素外排，同时细胞内蓄积增加。我们的研究结果表明，ONO - 1078通过抑制MRP功能来调节肺癌细胞的多药耐药性并抑制LTC4外排。
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