雄激素对耐多西他赛前列腺癌细胞P-gp、GST-π表达的影响

Effects of androgen on the expressions of P-glycoprotein and glutathione-S-transferase-π in docetaxel-resistant prostate cancers

目的 研究雄激素对耐多西他赛前列腺癌细胞P-糖蛋白（P-gp）、谷胱甘肽-S-转移酶-π（GST-π）表达的影响.方法 人前列腺癌细胞株LNCaP及PC-3在含多西他赛的培养液中诱导耐药细胞株（LNCaP/Docetaxel,PC-3/Docetaxel）,将耐药细胞株分别在含有二氢睾酮（DHT）培养液和含二氢睾酮＋比卡鲁胺培养液中培养7 d.免疫细胞化学法检测两组细胞P-gp、GST-π的表达水平.结果 经DHT诱导后,P-gp和GST-π在LNCaP/Docetaxel及PC-3/Docetaxel细胞系的表达明显升高（χ2＝7.367,6.874,P＜0.05）;而经DHT＋比卡鲁胺联合作用后,P-gp和GST-π的表达保持不变（P＞0.05）.结论 二氢睾酮可诱导耐多西他赛前列腺癌的耐药相关蛋白P-gp及GST-π增量表达,雄激素受体阻断剂比卡鲁胺可阻断二氢睾酮的诱导作用.

Objective To explore the relationship of P-glycoprotein （P-gp） and glutathione-S-transferase-pi （GST-π） ex- pressed in prostate cancer ceils that responded tO androgen. Methods LNCaP and PC-3 were exposed to be gradually increased do- cetaxel concentration, and muhidrug resistance cell lines （LNCaP/Docetaxel and PC-3/Docetaxel） were established. The multidrug re- sistance cell lines were cultured with dihydrotestosterone （ DHT）, or DHT and bicalutamide for 7 days. The expressions of P-gp and GST-π were observed with immunocytochemical method. Results Expressions of P-gp and GST-xr in LNCaP / Docetaxel and PC-3/ Docetaxel cell lines were significantly lower than those in cells induced with DHT （ X2 = 7. 367,6. 874, P 〈 0. 05 ）. There was no change in ceils cultured with DHT and bicalutamide （ P 〉 0.05 ）. Conclusions DHT upregulated the expressions of P-gp and GST-π in docetaxel-resistant prostate cancers, and bicalutamide blocked the effect of DHT.