| 摘要: |
| ［目的］探讨mdr1基因编码的P-糖蛋白（mdr1/P-gp）在阿霉素（ADR）诱导的卵巢癌多药耐药细胞中的作用。［方法］MTT法检测药物对敏感细胞株（SK-OV-3）和诱导的耐药细胞株（SK-OV-3/adr）的半数致死浓度（IC50），计算耐药指数（RI）和加逆转剂后的逆转倍数，荧光显微镜观察不同时间细胞内的药物含量变化，荧光分光光度法测定细胞内ADR的含量，RT-PCR和Western blot法检测细胞耐药前后mdr1/P-gp的变化。［结果］对阿霉素、长春新碱、紫杉醇和足叶乙甙，SK-OV-3/adr细胞株的IC50 均有明显增加，RI分别为58.4、122.6、41.0和43.7，逆转倍数分别为20.5、66.9、11.3和18.1。30、60、120 min SK-OV-3细胞株ADR含量分别是SK-OV-3/adr细胞株的3.7［（191.9±1.7）/（51.7±6.3）ng/mL］、5.9［（285.3±4.0）/（48.2±2.8）ng/mL］和8.6［（447.8±1.3）/（52.0±1.8）ng/mL］倍，二者比较差异有非常显著性意义（P<0.01）。P-gp竞争性逆转剂（Ver）作用30、60、120 min后SK-OV-3/adr细胞ADR含量提高了1.6、2.7和5.1倍，与逆转前相比差异有非常显著性意义（P<0.01）。RT-PCR和Western blot结果显示SK-OV-3/adr细胞mdr1/P-gp均表达阳性，SK-OV-3细胞mdr1/P-gp表达阴性。［结论］mdr1/P-gp在ADR诱导的SK-OV-3/adr细胞多药耐药机制中起重要作用。 |
| 关键词: 卵巢肿瘤 多药耐药 mdr1/P-gp |
| DOI：10.11724/jdmu.2010.01.09 |
| 分类号:R73-36 |
| 基金项目: |
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| Expression of P-glycoprotein induced by adriamycin in multidrug resistance cells of ovarian cancer |
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MIAO Ying-qiu1, LI Zhi2, GAO Wen-cang3
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1.Medical College, Dalian University, Dalian 116622, China;2.Department of Clinical Laboratory, Dalian Central Hospital, Dalian 116033, China;3.Department of Oncology, Xinhua Hospital of Dalian University, Dalian 116021, China
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| Abstract: |
| ［Objective］ To investigate the effect of P-glucoprotein (mdr1/P-gp) encoded by mdr1 gene on drug resistant cells of ovarian cancer induced by Adriamycin(ADR).［Methods］ MTT assay was employed to test the lethal concentration 50 (IC50) of sensitive germline (SK-OV-3) and ovarian cancer cell subline induced by ADR (SK-OV-3/adr) treated by 4 drugs, resistance index and reverse multiple were calculated. The changes of drug content were observed by fluorescence microscope, the intracellular accumulation of ADR was evaluated by fluorospectrophotometry, the changes of mdr 1/P-gp resistance were observed respectively by RT-PCR and Western blot.［Results］ After treatment of Adriamycin, Vincristine, Paclitaxel and Etoposide, the IC50 of SK-OV-3/adr increased significantly, the resistance indexes (RIs) were 58.4, 122.6, 41.0 and 43.7, respectively. ADR contents of SK-OV-3 detected by fluorospectrophotometry in 30min, 60min and 120 min were 3.7, 5.9, 8.6 times, respectively (SK-OV-3 vs SK-OV-3/adr, P<0.01). After treated by P-gp competively reverse agent (Ver) in 30 min, 60 min and 120 min ADR contents of SK-OV-3/adr were 1.6, 2.7 and 5.1 times higher (P<0.01). The mdr 1/P-gp expression of SK-OV-3/adr cell was observed by RT-PCR and Western blot, but lost in SK-OV-3 cell.［Conclusion］ mdr1/P-gp plays a role in the multidrug resistance of SK-OV-3/adr cell induced by ADR. |
| Key words: ovarian cancer multidrug resistance mdr1/P-gp |
