摘要
目的:探讨选择性环氧化酶-2(cy-clooxygenase-2,COX-2)抑制剂nimesulide对乳腺癌细胞株化疗敏感性的影响,同时探讨其可能机制。方法:利用体外培养的乳腺癌细胞株MDA-MB-231、MCF-7,MTT法比较多柔比星(ADM)及联合不同浓度的nimesu-lide对两种细胞抑制率的影响(IC50);应用逆转录聚合酶链反应(RT-PCR)观察不同浓度nimesulide对两种细胞多药耐药蛋白(MDR1)mRNA的影响。结果:Nimesulide能增加ADM对MDA-MB-231、MCF-7的细胞毒作用,这种作用与nimesulide呈剂量依赖性,对COX-2高表达的MDA-MB-231细胞更加敏感;nimesulide能降低MDR1mRNA的表达水平,并呈剂量依赖性(10、25、50μmol/Lnimesulide)。结论:选择性COX-2抑制剂nimesulide能增加ADM对MDA-MB-231、MCF-7的细胞毒作用,这种作用可能与MDR1水平的下调有关,为选择性COX-2抑制剂联合细胞毒药物用于乳腺癌的化疗提供了实验依据。
OBJECTIVE： To investigate the effect of selective COX-2 inhibitor nimesulide on the chemotherapy sensitiveness in breast cancer cell lines and to elucidate its possible mechanism. METHODS： MTT assay was used to compare the inhibiting rate IC50 in breast cancer MDA-MB-231 and MCF-7 cell line treated with adriamycin in combination with the different dose nimesulide, at the time MDR1 mRNA levels were measured by mean of reverse transcription polymerase chain reation. RESULTS： Nimesulide could enhance cytotoxicity of adriamycin in breast cancer MDA-MB-231 and MCF-7 cell line, and in dose-dependent manner. Comparisons of COX-2 expression with sensitivity to nimesulide suggest a substantial association between COX-2 expression level and sensitivity to nimesulide. Nimesulide could decrease the expression level of MDR1 mRNA does-dependently. CONCLUSIONS：Selective COX-2 inhibitor nimesulide could enhance cytotoxicity of adriamycin in breast cancer MDA-MB-231 and MCF-7 cell line, the mechanism may correlate with down-regulation of the expression level of MDR1 mRNA. It may be useful in the chemotherapy of human breast cancer by the combined use of a selective COX-2 inhibitor and conventional anticancer agents.
出处
《中华肿瘤防治杂志》
CAS
2006年第16期1214-1218,共5页
Chinese Journal of Cancer Prevention and Treatment
