Zhu L, Lang J, Shen K
Peking Union Hospital, Peking Union Medical College Chinese Academy of Medical Science, Beijing.
Zhonghua Fu Chan Ke Za Zhi. 1997 Aug;32(8):462-6.
To study the relationship between multi-drug-resistance (MDR1) gene expression and the drug resistance of ovarian carcinoma and the reversing potency of drug-resistance modifying agent--cyclosporin A (CsA).
Tumor-bearing mice of ovarian carcinoma cell (OVCA3) 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 MDR1 gene by means of RT-PCR.
Ovarian carcinoma cells with positive MDR1 gene expression showed cross drug-resistance to ADM, daunorubicin (DNR), vincristine (VCR) and etoposide (VP-16), the value of inhibiting concentration (IC50) is 4.1-15.5 times of that of the cells with negative MDR1 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 MDR1 gene expression and the pathologic type or differential grade. The possibility of poor prognosis of patients with positive MDR1, gene expression was 16.07 (1.78-144.7) times of that of patients with negative MDR1 gene expression.
MDR-related drug can induce the overexpression of MDR1 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 MDR1 gene expression in patients of ovarian carcinoma could be used as an index to predict the prognosis of the patients.
研究多药耐药(MDR1)基因表达与卵巢癌耐药性之间的关系以及耐药修饰剂——环孢素A(CsA)的耐药逆转效力。
将荷卵巢癌细胞(OVCA3)的小鼠随机分为三组:对照组、阿霉素(ADM)组和ADM + CsA组。观察并比较各组小鼠的肿瘤生长率和生存率。采用逆转录聚合酶链反应(RT-PCR)法检测32例卵巢癌患者冷冻组织标本中MDR1基因的表达。
MDR1基因表达阳性的卵巢癌细胞对ADM、柔红霉素(DNR)、长春新碱(VCR)和依托泊苷(VP-16)呈现交叉耐药,其半数抑制浓度(IC50)值是MDR1基因表达阴性细胞的4.1 - 15.5倍。对于荷瘤小鼠,CsA + ADM联合治疗组与单纯ADM治疗组小鼠的肿瘤生长率有显著差异(P<0.01)。在32例卵巢癌组织冷冻标本中,未证实MDR1基因表达与病理类型或分化程度之间存在关联。MDR1基因表达阳性患者预后不良的可能性是MDR1基因表达阴性患者的16.07(1.78 - 144.7)倍。
MDR相关药物可诱导MDR1基因的过度表达并导致多药耐药现象的出现。CsA在体外和体内均可部分逆转卵巢癌细胞的多药耐药性。检测卵巢癌患者MDR1基因表达可作为预测患者预后的指标。