他莫昔芬体外降低EAC/ADR细胞对阿霉素的耐药性

Tamoxifen reduced doxorubicin resistance in EAC/ADR cell in vitro

目的研究他莫昔芬体外降低EAC／ADR细胞对阿霉素耐药性的作用及耐药性与细胞膜流动性的相关性。方法细胞内谷胱甘肽含量及细胞膜流动性分别以荧光分光光度法及荧光偏振法测定，细胞存活力以甲基四唑蓝法测定。结果EAC／ADR细胞膜流动性及谷胱甘肽含量均比敏感EAC细胞明显提高。他莫昔芬2mg·L-1及5mg·L-1不影响EAC／ADR细胞谷胱甘肽含量（P＞0.05），但可明显降低其细胞膜流动性（P＜0.05）。他莫昔芬2mg·L-1或5mg·L-1与阿霉素体外合用于EAC／ADR细胞可降低其对阿霉素的耐药性，同时发现他莫昔芬不影响阿霉素对敏感EAC细胞的毒性。结论EAC／ADR细胞膜流动性增加与其对阿霉素的耐药性有着密切关系，他莫昔芬在降低EAC／ADR细胞膜流动性的同时降低细胞对阿霉素的耐药性。

AIM To study the effect of tamoxifen (Turn) reducing doxorubicin (Dox) resistance in EAC/ADR cells in vitro, and the correlation of drug resistance with cell membrane fluidity. METHODS Glutathione (GSH) content and cell membrane fluidity were measured by fluorometric assay and fluorescence depolarization assay, respectively. Cell viability was determined by 3-(4, 5-dimethylthiazol )-2, 5-diphenyltetrazolium bromide assay. RESULTS Cell membrane fluidity and GSH content of EAC/ADR cells were both higher than those in sensitive EAC cells. Tam 2 mg· L-1 and 5 mg· L-1 had no obvious effect on GSH content in EAC/ADR cells (P＞0. 05), but it decreased the elevated membrane fluidity efficiently(P＜0. 05). The simultaneous incubation of Dox with Turn 2 mg· L-1 or 5 mg· L-1 in EAC/ADR cells reduced Dox resistance, no same effect of Turn was observed in drug-sensitive EAC cell. CONCLUSION The elevated membrane fluidity in EAC/ADR cell is correlated with Dox resistance tightly. Tam reduces Dox resistance in EAC/ADR cells while cell membrane fluidity is decreased.