多药耐药基因反义寡脱氧核苷酸对卵巢癌细胞株SKOV3多药耐药性逆转的作用  

Study of Mdr1 Antisense Oligodeoxynucleotides on Reversal of Multidrug Resistance in Ovarian Carcinoma Cell Line SKOV3

作　　者：童英[1] 潘凌亚[1] 周生[2] 吴英[2] 毛宁[2] 杨秀玉[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,100730 [2]军事医学科学院基础医学研究所

出　　处：《中华妇产科杂志》2000年第11期677-679,共3页Chinese Journal of Obstetrics and Gynecology

摘　　要：目的　探讨多药耐药基因 (mdr1)反义寡脱氧核苷酸 (ASON)对卵巢癌细胞多药耐药性的逆转作用。方法　以人mdr1基因转导产生的耐药卵巢癌SKOV3/mdr1细胞为模型 ,采用 2 5 0 μg/mlmdr1 ASON ,作用于SKOV3/mdr1细胞 ,采用流式细胞术及罗丹明 12 3排出试验 ,检测SKOV3/mdr1细胞mdr1基因产物P 糖蛋白 (P gp)的阳性率及其功能。并进行SKOV3/mdr1细胞集落培养 ,观察耐药性。结果　mdr1 ASON作用后 ,SKOV3/mdr1细胞的P gp阳性率由 38 9%减少至 2 1 3% (P <0 0 1) ,SKOV3/mdr1细胞内罗丹明的潴留率 ,由 32 1%增加至 5 0 7% (P <0 0 1)。SKOV3/mdr1细胞加mdr1 ASON和空白对照细胞形成抗性细胞集落的相对百分数 ,在泰素浓度达 5ng/ml时 ,分别为 8%和 6 3%(P <0 0 1) ,在阿霉素浓度达 10 0ng/ml时 ,分别为 34 %和 79% (P <0 0 1)。结论　mdr1 ASON可一定程度的逆转卵巢癌细胞多药耐药性 ,从而提高卵巢癌细胞对化学治疗药物的敏感性。Objective To investigate the effect of mdr1 antisense oligodeoxynucleotides (ASON) on reversal of multidrug resistance in ovarian carcinoma cells. Methods Drug resistance ovarian carcinoma cells SKOV3/mdr1 transducted with human multidrug resistance gene (mdr1) were served as models. The positive rate and function of the mdr1 gene product P glycoprotein (P gp) in SKOV3/mdr1 cells after mdr1 ASON (250 μg/ml) treatment were determined by flow cytometry and rhodamine 123 efflux trial. Drug resistance of SKOV3/mdr1 cells was also observed by cell colony culture. Results P gp positive rate of SKOV3/mdr1 cells after mdr1 ASON treatment was decreased from 38 9% to 21 3% ( P< 0 01). Intracellular rhodamine retension in SKOV3/mdr1 cells after mdr1 ASON treatment was increased from 32 1% to 50 7% ( P< 0 01). Under effect of Taxol 5 ng/ml, the relative percents of drug resistant colony in mdr1 ASON treated SKOV3/mdr1 cells and in SKOV3/mdr1 cells was 8% and 63%, respectively, ( P< 0 01). Under effect of Doxorubicin 100ng/ml, the relative percents of drug resistant colony in mdr1 ASON treated SKOV3/mdr1 cells and in SKOV3/mdr1 cells was 34% and 79%, respectively, ( P< 0 01). Conclusion mdr1 ASON can reverse multidrug resistance of ovarian carcinoma cell in a certain extent so as to increase chemotherapeutic sensitivity of ovarian carcinoma cells.

关 键 词：卵巢肿瘤 MDR1基因 ASON 多药耐药性 

分 类 号：R737.31[医药卫生—肿瘤]