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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。
OBJECTIVE: To establish a cisplatin-resistant cell line 3AO / CDDP to evaluate the clinical characteristics of chemotherapy in ovarian epithelial carcinoma. The expressions of LRP, MRP, P-gp, GSTπ and TopeⅡ were detected. Methods: The minimum dose of chemotherapy for ovarian epithelial carcinoma was used to calculate the final concentration. Cisplatin resistant cell lines were established by repeated intermittent 24h exposure with high dose of cisplatin (10μg / ml). The expression of LRP, MRP, P- gp, GSTπ and Topo II expression. Results: The resistance to cisplatin-resistant 3AO / cDDP was completed in 4.5 months. The resistance index was 1.62, which was similar to that of clinical drug resistance. Compared with 3AO, the expression of MRP and P-gp in 3AO / cDDP cells did not change significantly (P> 0.05), and the expressions of LPR and GSTπ were significantly increased (P <0.005 and P <0.05) Significantly lower (P <0.05). Conclusions: 3A0 / cDDP is established by simulating the characteristics of clinical drug use, and is an ideal model for cisplatin resistance. Cisplatin resistance is related to the increase of LRP and GSTπ expression and the decrease of Topo Ⅱ content, but not to MRP and P-gp.