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

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。

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

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.