Xu C J, Zhang Y, Wang J, Zhang T M
Department of Pharmacology, He-nan Institute of Medical Science, Zhengzhou, China.
Zhongguo Yao Li Xue Bao. 1998 May;19(3):273-6.
To study the effect of menadione (Men) reducing doxorubicin (Dox) resistance in Ehrlich ascites carcinoma (EAC) cells resistant to Dox (EAC/Dox cells).
Glutathione (GSH) content and membrane fluidity were measured by fluorometric assay and fluorescence depolarization assay, respectively. Glutathione S-transferase (GST) activity was measured with 1-chloro-2,4-dinitrobenzene as the substrate. Cell viability was determined by 3-(4, 5-dimethylthiazol)-2, 5-diphenyltetrazolium bromide assay.
GSH content, GST activity, and membrane fluidity in EAC/Dox cells were higher than those in EAC cells (P < 0.01). The IC50 (95% confidence limits) for Dox on EAC/Dox cell was 22.3 (15.8-28.8) mg.L-1. Relative resistance of Dox in EAC/Dox cells was 42-fold. Pretreatment of EAC/Dox cells with Men 5 or 10 mg.L-1 decreased intracellular GSH content (P < 0.01). Men 1 mg.L-1 had no obvious effect on GSH content in EAC/Dox cells (P > 0.05), but decreased the elevated membrane fluidity efficiently (P < 0.05). Men had no obvious effect on GST activity in EAC/Dox cells (P > 0.05). IC50 of Dox was reduced to 9.6 (7.8-11.3), 6.0 (2.8-9.2), or 5.3 (3.9-6.7) mg.L-1 in EAC/Dox cells pretreated with Men 1, 5, or 10 mg.L-1.
Men reduced Dox resistance effectively due in part to its depletion of GSH content in EAC/Dox cells.
研究甲萘醌（Men）降低多柔比星（Dox）耐药的艾氏腹水癌（EAC）细胞（EAC/Dox细胞）对多柔比星（Dox）耐药性的作用。
分别采用荧光分析法和荧光偏振分析法测定谷胱甘肽（GSH）含量和膜流动性。以1-氯-2,4-二硝基苯为底物测定谷胱甘肽S-转移酶（GST）活性。采用3-(4,5-二甲基噻唑)-2,5-二苯基四氮唑溴盐法测定细胞活力。
EAC/Dox细胞中的GSH含量、GST活性和膜流动性均高于EAC细胞（P<0.01）。Dox对EAC/Dox细胞的半数抑制浓度（IC50，95%置信区间）为22.3（15.8 - 28.8）mg·L-1。EAC/Dox细胞对Dox的相对耐药倍数为42倍。用5或10 mg·L-1的Men预处理EAC/Dox细胞可降低细胞内GSH含量（P<0.01）。1 mg·L-1的Men对EAC/Dox细胞中的GSH含量无明显影响（P>0.05），但能有效降低升高的膜流动性（P<0.05）。Men对EAC/Dox细胞中的GST活性无明显影响（P>0.05）。在用1、5或10 mg·L-1的Men预处理的EAC/Dox细胞中，Dox的IC50分别降至9.6（7.8 - 11.3）、6.0（2.8 - 9.2）或5.3（3.9 - 6.7）mg·L-1。
Men能有效降低Dox耐药性，部分原因是其降低了EAC/Dox细胞中的GSH含量。
