甲孕酮逆转卵巢癌多药耐药的研究  

Medroxyprogesterone on the reversal of multidrug resistance in ovarian cell line

作　　者：薛昀[1] 尤宗兵[1] 郭燕燕[1] 段海鸥 廖秦平 

机构地区：[1]北京医科大学第一附属医院妇产科,100034

出　　处：《中国实用妇科与产科杂志》2000年第9期541-544,共4页Chinese Journal of Practical Gynecology and Obstetrics

基　　金：卫生部科学研究基金资助!(编号类 :96-1-2 80 )

摘　　要：目的　研究甲孕酮 (medroxyprogesteroneacetate ,MPA)对卵巢癌耐药细胞系SKOV - 3多药耐药基因MDR1的表达和功能的影响及对多药耐药的逆转作用。方法　采用半定量逆转录聚合酶链反应方法 ,研究在不同浓度和作用时间下 ,甲孕酮对SKOV - 3细胞MDR1mRNA表达的影响 ,采用流式细胞术检测单加阿霉素、甲孕酮联合阿霉素及异搏定联合阿霉素时 ,细胞内阿霉素浓度 ,采用裸鼠腹水瘤模型 ,研究甲孕酮辅助化疗对荷瘤裸鼠生存时间与生存率的影响。结果　在不同浓度和不同作用时间下 ,甲孕酮对SKOV - 3细胞MDR1mRNA的表达无影响 ;甲孕酮能显著增加细胞内阿霉素浓度 ,且增加幅度与异搏定相似 ;甲孕酮联合阿霉素可使裸鼠平均生存时间比其他治疗组延长 ,生存率也有改善 ,但无统计学意义。结论　甲孕酮不能调控SKOV - 3细胞MDR1mRNA的表达 ,但能促使胞内阿霉素浓度增加 ,其与阿霉素联合用药对荷瘤裸鼠生存时间和生存率有一定改善 ,但无统计学意义。Objectvie\ To study the effects of medroxyprogesterone on the expression and function of human multidrug resistance gene(MDR1)in drug-resistance SKOV-3 cell line and reversal of the multidrug resistance.Method\ Semiquantitative RT-PCR was used to measure the MDR1 mRNA expression of SKOV-3 cells treated with medroxyproge sterone under different concentration and treated time.Intracellular concentration of doxorubicin was detected by flow cytometry during the treatment of doxorubicin alone,or in combination with medroxyprogesterone or verapamil.Intraabdominal xenograft model of human ovarian cancer was established by i.p.injection of SKOV-3 cells in female nude athymic mice,the survival time and rate of which were compared among the groups with or with out medroxgprogesterone accessory treatment in vivo.Results\ MDR1 mRNA expression of SKOV-3 cells was not affected by medroxyprogesterone,either at different concentrations or for different periods.Medroxyprogesterone significantly increased the intracellular accumulation of doxorubicin in SKOV-3 cells,the increment of which was similar to that of verapamil.In vivo,the survival time and rate of tumor-bearing mice treated with medroxyprogesterone or adriamycin alone were not improved significantly.The tumor-bearing mice treated with medroxyprogesterone and adriamycin in combination lived on the average six days longer and with better survival rate than those treated otherwise,but the difference was not statistically significant.Conclusion\ Medroxyprogesterone can not regulate the MDR1 mRNA expression of SKOV-3 cells,but it can increase the intracellular concentration of doxorubicin, probably by inhibition of drug efflux by p-glycoprotein.Medroxyprogesterone combined with adriamycin can improve the survival time and rate of adriamycin-resistant tumorbearing mice,though not statistically significant.

关 键 词：多药耐药性 P糖蛋白 甲孕酮 卵巢肿瘤 

分 类 号：R737.310.5[医药卫生—肿瘤]