乳腺癌组织COX-2表达及其与肿瘤多药耐药关系的研究  

Expressin of cyclooxygenase-2 in breast cancer tissues and its relationship with multidrug resistance

作　　者：张玲[1] 陈同钰[1] 田波[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：《中华肿瘤防治杂志》2008年第19期1454-1457,共4页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的:通过观测环氧合酶-2(COX-2)抑制剂尼美舒利(Nimesulide)对人乳腺癌细胞株MDA-MB-231的化疗药物敏感性及其对P-糖蛋白(P-gp)表达的影响,探讨COX-2对乳腺癌细胞多药耐药(MDR)的调节作用。方法:以乳腺癌细胞株MDA-MB-231为研究对象,用MTT法研究COX-2抑制剂Nimesulide单独及联合不同浓度的丝裂霉素(MMC)对MDA-MB-231的抑制作用(IC50),流式细胞技术检测细胞凋亡率及COX-2和P-gp的表达变化。结果:MMC单独作用于乳腺癌细胞株MDA-MB-231,MMC对细胞的IC50为8.59±1.16,25μmol/L的Nimesulide与MMC联合作用,IC50减少5.89±0.66,差异有统计学意义,P=0.002;50μmol/L的Nimesulide与MMC联合作用,IC50进一步减少3.31±0.30,与25μmol/L比较,差异有统计学意义,P=0.003。说明Nimesulide能增加MMC对MDA-MB-231的化疗敏感性,这种作用与Nime-sulide呈剂量依赖性。流式细胞仪分析发现,Nimesulide可诱导细胞凋亡,且随着浓度的增加,凋亡率也随之增加(由0.13±0.15增加到29.2±0.95),差异有统计学意义,F=44.84,P=0.000。Nimesulide作用于MDA-MB-231细胞后,COX-2和P-gp的表达同时下降,COX-2的表达由70.37±1.98降低为9.60±2.11,P-gp的表达由14.13±2.63降低为0.43±0.15,差异均有统计学意义,P值均<0.05。结论:Nimesulide能明显增加MMC对乳腺癌细胞株MDA-MB-231的化疗敏感性,COX-2与肿瘤MDR密切相关,且可能通过P-gp来实现。OBJECTIVE： To explore the role of COX-2 in mediation of muhidrug resistance in breast cancer by studying the effect of selective COX-2 inhibitor Nimesulide on breast cancer MDA-MB-231 and its effect on the expression of P-gp. METHODS： Human breast cancer MDA-MB-231 was taken as the target to investigate the effect of COX-2 inhibitor Nimesulide on the rate of apoptosis and the expressions of COX-2 and P-gp by flow cytometry. MTT assay was used to compare the inhibiting rate IC50 in breast cancer MDA-MB-231 cell line treated with Nimesulide alone or in combination with the different doses of Mitomycin. RESULTS：The cell line was treated with Mitomyein alone, and IC50 of MMC to cell line was 8.59 ± 1.16, and the cell line was treated with 25 umol/L Nimesulide in combination with MMC, and IC50 was 5.89±0.66, P=0. 002. The cell line was treated with 50 umol/L Nimesulide in combination with MMC, and ICs0 was 3.31±0.30, P=0. 003. It suggested nimesulide enhanced the chemotherapy sensitivity of mitomycin in breast cancer MDA-MB-231 in a dose-dependent man- ner in vitro. Flow cytometry showed nimesulide stimulated the apoptosis of MDA-MB-231 cell in dose-dependent manner （0.13±0.15→29.2±0.95）,F=44.84, P=0. 000. Nimesulide decreased the expressions of COX-2 and P-gp in dose -dependent manner. The expression of COX-2 was decreased from 70.37±1.98 to 9. 60±2. 11 and the expression of P-gp was decreased from 14.13±2.63 to 0.43±0.15,P〈0.05. CONCLUSIONS： Nimesulide can enhance the cytotoxicity of mitomycin in breast cancer MDA-MB-231 cell line. COX-2 is closely related to multdrug resistance, and perhaps it regulates the effect of multidrug resistance by P-gp.

关 键 词：乳腺肿瘤 丝裂霉素 磺胺类 前列腺素内过氧化物合酶 

分 类 号：R737.9[医药卫生—肿瘤]