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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 |
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童英 潘凌亚 周生 吴英 毛宁 杨秀玉
【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250 μg/ml mdr1-ASON，作用于SKOV3/mdr1细胞，采用流式细胞术及罗丹明123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21.3%(P<0.01),SKOV3/mdr1细胞内罗丹明的潴留率，由32.1%增加至50.7% (P<0.01)。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5 ng/ml时，分别为8%和63%(P<0.01)，在阿霉素浓度达100 ng/ml时，分别为34%和79% (P<0.01)。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。
【关键词】 寡核甘酸类，反义； 卵巢肿瘤； P-糖蛋白； 基因，MDR
Study of Mdr1 Antisense Oligodeoxynucleotides on Reversal of Multidrug Resistance in Ovarian Carcinoma Cell Line SKOV3
TONG Ying*, PAN Lingya, ZHOU Sheng, et al
（Department of Obstetrics and Gynecology, General Hospital of Air Force, People′s Liberation Army, Beijing 100036, China）
【Abstract】 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 perce[1] [2] [3] 下一页
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