Cox-2在乳腺癌多药耐药中的作用及其与P-gp、MRP1的关系  

Role of cyclooxygenase-2 in multidrug resistance of breast cancer and relationship with P-gp and MRP1

作　　者：田波[1] 陈铜兵[1] 鲁常青[1] 陈同钰[1] 

机构地区：[1]苏州大学附属第三医院病理科,江苏常州213003

出　　处：《实用肿瘤杂志》2010年第5期542-545,共4页Journal of Practical Oncology

摘　　要：目的通过检测环氧合酶-2(cyclooxygenase-2,Cox-2)抑制剂尼美舒利(nimesulide)对人乳腺癌细胞株MDA-MB-231的对化疗药物敏感性及其对P-gp、MRP1表达的影响,探讨Cox-2在乳腺癌细胞肿瘤多药耐药(multidrug resistance,MDR)中的作用及其作用机制。方法 (1)MTT法检测丝裂霉素(MMC)及其与不同浓度Cox-2抑制剂nimesulide联合作用对MDA-MB-231的抑制作用(IC50);(2)流式细胞术检测不同浓度nimesulide作用后,细胞凋亡率的变化及Cox-2、P-gp、MRP1的表达情况。结果 (1)以25、50μmol/L的nimesulide与MMC联合作用,MDA-MB-231细胞的IC50值(5.89±0.66、3.31±0.30)小于MMC单独作用的IC50值(8.59±1.16)且呈剂量依赖性,差异有统计学意义;(2)nimesulide可诱导细胞凋亡,且随着浓度的增加,凋亡率也随之增加(0.13±0.15至29.2±0.95),差异有统计学意义;(3)25、50μmol/L nimesulide作用于MDA-MB-231细胞后,Cox-2、P-gp、MRP1的表达值均下降。结论 nimesulide能增加乳腺癌细胞株MDA-MB-231对化疗的敏感性,诱导细胞凋亡;Cox-2参与肿瘤多药耐药(MDR),且可能通过影响P-gp、MRP1的表达来实现。Objective To investigate the role of Cox-2 in the multidrug resistance of breast cancer by studying the effect of Cox-2 inhibitor nimesulide on chemotherapy sensitivity of breast cancer MDA-MB-231 cells and its effect on the expression of P-glycoprotein and MRP1.Methods（1）MTT assay was used to compare the inhibiting rate IC50 in breast cancer MDA-MB 231 cell line treated with mitomycin alone or with mitomycin in combination with different doses of nimesuli.（2）The effection of nimesulide on apoptosis and the expression of Cox-2,P-gp was investigated by flow cytometry.Results（1）Compared with MDA-MB-231 cells explored to MMC alone（8.59±1.16）,the IC50 of MDA-MB 231 cells decreased after combined with 25 and 50 μmol/L of nimesulide（5.89±0.66,3.31±0.30）,and in a dose dependent manner in vitro.（2）It was showed that nimesulied could stimulate apoptosis of MDA-MB 231 cells and in a dose dependent manner（from 0.13±0.15 to 29.2±0.95）.（3）Explored to 25 and 50 μmol/L of nimesulide,the expressions of Cox-2,P-gp and MRP1 decreased.Conclusions Nimesulide could enhance chemotherapy sensitivity of mitomycin and stimulate apoptosis in breast cancer MDA-MB-231 cell line.Cox-2 takes part in multidrug resistance of breast cancer,and perhaps it realizes the effect by regulating the expression of P-gp and MRP1.

关 键 词：乳腺肿瘤/病理学 前列腺素内过氧化物合酶 基因 MDR 尼美舒利/治疗应用 糖蛋白类 细胞凋亡 

分 类 号：R737.9[医药卫生—肿瘤]