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人卵巢上皮性癌顺铂耐药细胞系3AO/cDDP模型的建立及耐药机理的实验研究

Establishment of cisplatin-induced resistant human ovarian epithelial cancer cell line 3AO/cDDP and experimental study on its resistant mechanisms

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【作者】 陈建利江森杨瑞芳刘福生孙晓明

【Author】 Chen Jianli; Jiang Sen; Yang Ruifang; et al. (The Affiliated Hospital of Shandong Medical University, Jinan 250012)

【机构】 山东医科大学附属医院妇产科!250012上海医科大学妇产科医院首都医科大学神经外科研究所解放军济南军区总医院

【摘要】 目的:模拟临床卵巢上皮性癌化疗的用药特点建立顺铂耐药细胞系3AO/CDDP,检测LRP、MRP、P-gp、GSTπ和TopeⅡ表达。方法:以临床卵巢上皮性癌化疗用药的最低剂量换算终浓度,采用大剂量顺铂(10μg/ml)反复间歇24h暴露法建立顺铂耐药细胞系;用FCM法检测LRP、MRP、P-gp、GSTπ和TopoⅡ表达。结果:历时4.5个月建成顺铂耐药株3AO/cDDP,耐药性稳定,耐药指数1.62,与临床耐药倍数相近。3AO/cDDP细胞MRP、P-gp表达与3AO相比无明显变化(P>0.05),LPR、GSTπ表达明显升高(P<0.005及P<0.05),Tope-Ⅱ含量明显降低(P<0.05)。结论:3A0/cDDP是模拟临床用药特点建立的、研究顺铂耐药的理想模型;顺铂耐药与LRP、GSTπ表达升高及TopoⅡ含量降低有关,与MRP、P-gp无关。

【Abstract】 Objective: To establish cisplatin - induced resistant ovarian cancer cell line 3AO/cDDP, and to detect expressions of LRP, MRP, P - gp. GSTπ and Topo Ⅱ. Methods: Using the corresponding dose calculated from clinical chemotherapy, 3 AO/ cDDP was established,with 3Ao exposed intervally and repeatedly to high - level concentration of cisplatin at 10μg/ml for 24 hours each time. LRP, MRP, P - gp, GSTπ and Topo Ⅱ expressions were detected with FCM. Results: 3 AO/cDDP was estabished after 4. 5 months with stable resistance and resistance index 1 .62 which was similar to clinical resistant degree. tow expression levels of MRP and P - gp were found in both 3AO/cDDP and 3Ao, and no statistical difference between the two lines(P >0 .05 ). However, LRP and GSTπ expression levels in 3AO/cDDP were significantly higher than those in 3Ao with FCM detection(P < 0. 005 and P < 0. 05 ), and Topo Ⅱ in 3AO/cDDP was lower(P < 0. 05 ). Conclusions: 3AO/cDDP, induced by cisplatin and imitating the characteristics of clinical chemotherapy for patients with ovarian epithelial cancer, is an ideal model for investigation of cisplatin resistance. Cisplatin resistance in 3AO/cDDP can be accounted for by higher LRP and GSTπ and lower Topo Ⅱ expressions and is not associated with MRP or P - gp.

  • 【文献出处】 现代妇产科进展 ,CURRENT ADVANCES IN OBSTETRICS AND GYNECOLOGY , 编辑部邮箱 ,2000年03期
  • 【分类号】R737.31
  • 【被引频次】4
  • 【下载频次】101
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