乳腺癌耐受蛋白的表达与5-氟尿嘧啶耐受的相关性研究  

Study on the relationship between breast cancer resistance protein expression and 5-fluorouracil resistance

作　　者：袁建辉[1] 程锦泉[1] 柯跃斌[1] 姬娜娜[1] 周建孟[1] 周丽[1] 黄海燕[1] 杨淋清[1] 刘建军[1] 徐新云[1] 庄志雄[1] 

机构地区：[1]深圳市疾病预防控制中心毒理研究室,518020

出　　处：《中华预防医学杂志》2008年第7期506-510,共5页Chinese Journal of Preventive Medicine

基　　金：国家自然科学基金（30500599）

摘　　要：目的筛选乳腺癌耐受蛋白（BCRP）介导的耐受药物，探讨BCRP的表达与耐受药物的相关性。方法采用已成功建立的BCRP表达细胞模型，经细胞存活实验（MTT法）筛选出BCRP介导的耐受药物，并利用高效液相色谱法（HPLC）测定细胞内残留耐受药物的相对含量；运用荧光定量逆转录-聚合酶链反应（RT-PCR）和免疫组织化学方法（IHC）检测140例临床乳腺癌组织标本中BCRP的表达，同时利用MTT法研究临床组织标本对耐受药物的化学敏感性；采用单项方差统计学检验方法分析临床乳腺癌组织中BCRP的表达与药物耐受的相关性。结果MTT实验结果显示，细胞对5．氟尿嘧啶（5-Fu）的耐药指数随着BCRP表达的升高而增加，达到10．58倍（P〈0．05，n=3）。HPLC实验证实BCRP的表达与细胞内残留的5-Fu呈显著的负相关性（r=-0．897，P〈0．05）。140例临床乳腺癌组织标本中，BCRP阳性表达率为33％（47／140）。BCRP阳性表达的乳腺癌组织对5-Fu的耐药指数是正常癌旁组织的7—12倍，BCRP的表达与5-Fu的耐受具有正相关性（R^2=0．8124，P〈0．01）。结论BCRP的表达与5．Fu的药物耐受具有显著的相关性，研究结果有助于BCRP阳性表达的乳腺癌病人化疗方案的制订和优化。Objective To screen breast cancer resistance protein BCRP-mediated resistance agents and to investigate the relations between BCRP expression and drug resistance. Methods MTI＂ assay was performed to screen BCRP-mediated resistant agents with established BCRP expression cell model. While, the high performance liquid chromatography（HPLC） assay was administrated to measure the related dosage of intracellular retention resistant agents. The BCRP expression was investigated by both real-time RT-PCR and immunohistochemistry（IHC） assay in 140 clinical breast cancer tissue specimens. Chemosensitivity to resistant agents for clinical breast cancer tissue specimens was analyzed by MTT assay. The Nonparametric variance statistics method was used to analyze the correlations between chnical breast cancer tissue of BCRP expression and drug resistance. Results MTT assay showed that increasing resistance of 5-fluorouracil （5- Fu） climbed with the increases of the BCRP expressions by 10. 58 times （ P 〈 0. 05, n = 3 ） in cell model. HPLC assay also proved that a significant negative correlation between the intracellular retention dose of 5-Fu with different expression of BCRP（ r = - 0. 897, P 〈 0. 05, n = 3 ）. Forty-seven tissue specimens of BCRP-positive expression were rapidly determined by using both real-time RT-PCR and IHC in 140 clinical breast cancer tissue specimens. Subsequently, the resistance index （RI） for 47 BCRP-positive clinical breast cancer tissues to 5-Fu was shown from 7 to 12 times compared with normal cancer-side tissues through MTT assay. The statistical correlation between BCRP expression and 5-Fu resistance was observed in clinical breast cancer tissue specimens（R2 = 0. 8124, P 〈 0. 01 ）. Conclusion This study results showed that there is a significant relationship between BCRP expression and 5-Fu resistance. Moreover, the results suggest that the chemotherapy scheme could be optimized on BCRP-positive expression breast cancer patients.

关 键 词：乳腺癌耐受蛋白 氟尿嘧啶 乳腺肿瘤 抗药性 肿瘤 

分 类 号：R686[医药卫生—骨科学]