卵巢上皮性癌顺铂耐药细胞株的建立及其多药耐药蛋白的表达

Establishment of Cisplatin induced Multidrug Resistant Human Epithelial Ovarian Cancer Cell Line 3AO/cDDP and Its Expressions of Multidrug Resistance Proteins

目的 以较大剂量和反复间歇用药的方式建立卵巢上皮性癌顺铂 (cDDP)耐药细胞株3AO/cDDP ,并检测其肺耐药蛋白 (LRP)、多药耐药相关蛋白 (MRP)和P 糖蛋白 (P gp)的表达。方法 以卵巢上皮性癌化学治疗用药的最低剂量换算终浓度 ,采用大剂量cDDP(10 μg/ml)反复间歇 2 4h暴露法建立 3AO/cDDP细胞株 ;用流式细胞仪 (FCM)检测LRP、MRP和P gp的表达。结果 历时 4.5个月建成 3AO/cDDP细胞株 ,耐药性稳定 ,耐药指数为 1.6 2 ,与临床耐药指数相近。FCM检测MRP、P gp的表达 ,3AO/cDDP与 3AO相比 ,差异无显著性 (P >0 .0 5 ) ,LRP的表达明显升高 (P <0 .0 1)。结论 3AO/cDDP是以不同的诱导方式建立起来的对cDDP耐药的卵巢上皮性癌细胞株模型 ;3AO/cDDP的cDDP耐药与LRP表达升高有关 ,而与MRP、P

Objective To establish multidrug resistant ovarian cancer cell line 3AO/cDDP by exposing parent cell line intervally and repeatedly to high level concentration of cisplatin,and to detect expressions of lung resistance protein (LRP),multidrug resistance associated proterin(MRP) and P glycoprotein (P gp). Methods Using the corresponding dose calculated from clinical chemotherapy,we established 3AO/cDDP,with 3AO exposed intervally and repeatedly to high level concentration of cisplatin at 10 μg/ml for 24 hours each time; LRP、MRP and P gp expressions were detected with flow cytometry(FCM). Results 3AO/cDDP was established after 4.5 months with stable resistance and the drug resistant index was 1.62 which was similar to clinical resistance degree. Low expression levels of MRP and P gp were found in both 3AO and 3AO/cDDP, and no statistical difference between the two lines( P >0.05).However, LRP expression level in 3AO/cDDP was significantly higher than that in 3AO with FCM detection( P <0.01). Conclusions 3AO/cDDP,induced by exposing 3AO to high level concentration of cisplatin intervally and repeatedly, is an ideal model for investigation of cisplatin resistance.Cisplatin resistance in 3AO/cDDP could be related to high LRP expression and be not associated with MRP or P gp.