多药耐药基因表达与卵巢癌耐药关系的研究  

The Relationship between Multi Drug Resistance Gene Expression and Drug Resistance of Ovarian Carcinoma

作　　者：朱玲[1] 郎景和[1] 沈铿[1] 冷金花[1] 刘文淑[1] 许秀英[1] 

机构地区：[1]中国医学科学院中国协和医科大学北京协和医院妇产科

出　　处：《中华妇产科杂志》1997年第8期462-466,共5页Chinese Journal of Obstetrics and Gynecology

摘　　要：目的：探讨多药耐药（ＭＤＲ１）基因表达与卵巢癌耐药的关系以及耐药修饰剂——环孢素Ａ（ＣｓＡ）对卵巢癌耐药性的逆转影响。方法：建立裸鼠卵巢癌模型，随机分为对照组、阿霉素（ＡＤＭ）组、ＡＤＭ＋ＣｓＡ组，观察３组的肿瘤生长情况以及生存率。利用逆转录聚合酶链反应（ＲＴ－ＰＣＲ）方法检测３２例卵巢癌患者肿瘤组织ＭＤＲ１基因的表达情况。结果：ＭＤＲ１基因表达阳性的卵巢癌细胞对阿霉素、柔红霉素、足叶乙甙、长春新碱等多种化疗药物交叉耐药，其５０％细胞抑制浓度（ＩＣ５０值）是ＭＤＲ１基因表达阴性细胞的４．１～１５．５倍。当ＡＤＭ与ＣｓＡ联合应用后，裸鼠肿瘤生长速度与单用ＡＤＭ者之间的差异有显著性（Ｐ＜０．０１）。３２例卵巢癌患者ＭＤＲ１基因表达与卵巢癌的病理类型、分化程度之间没有明显的关系，而ＭＤＲ１基因表达阳性患者预后不良的机率是阴性患者的１６．０７（１．７６～１４４．７）倍。结论：ＭＤＲ１基因相关药物可以诱导ＭＤＲ１基因的过度表达，出现多药耐药的表型。ＣｓＡ可以在体外环境及动物体内环境中部分逆转卵巢癌细胞的耐药性。在卵巢癌患者中检测ＭＤＲ１基因的表达，可以作为判断临床预后的一个指标。Objective: To study the relationhsip between multi drug resistance (MDR 1) gene expression and the drug resistance of ovarian carcinoma and the reversing potency of drug resistance modifying agent——cyclosporin A (CsA). Methods: Tumor bearing mice of ovarian carcinoma cell (OVCA 3) were divided randomly into three groups: control group, adriamycin (ADM) group and ADM+CsA group. The tumor growth rate and the survival rate of mice were investigated and compared among the groups. 32 frozen specimens of ovarian carcinoma tissue from patients were examined for the expression of MDR 1 gene by means of RT PCR. Result: ovarian carcinoma cells with positive MDR 1 gene expression showed cross drug resistance to ADM, daunorubicin (DNR), vincristine (VCR) and etoposide (VP 16), the value of inhibiting concentration (IC 50 ) is 4.1～15.5 times of that of the cells with negative MDR 1 gene expression. To tumor bearing mice, there was significant difference in tumor growth rate between mice given combined therapy of CsA+ADM and those given ADM only ( P <0.01). Of the 32 frozen specimens of ovarian carcinoma tissue, there was no confirmed relationship between MDR 1 gene expression and the pathologic type or differential grade. The possibility of poor prognosis of patients with positive MDR 1 gene expression was 16.07(1.78～144.7) times of that of patients with negative MDR 1 gene expression. Conclusion: MDR related drugs can induce the overexpression of MDR 1 gene and result in the appearance of the multidrug resistance phenomenon. CsA can partially reverse the multidrug resistance of ovarian carcinoma cells both in vitro and in vivo. Detection of MDR 1 gene expression in patients of ovarian carcinoma could be used as an index to predict the prognosis of the patients.

关 键 词：抗药性 MDR1 基因表达 卵巢肿瘤 环孢素A 

分 类 号：R737.31[医药卫生—肿瘤]