中华预防医学杂志
中華預防醫學雜誌
중화예방의학잡지
CHINESE JOURNAL OF
2008年
7期
506-510
,共5页
袁建辉%程锦泉%柯跃斌%姬娜娜%周建孟%周丽%黄海燕%杨淋清%刘建军%徐新云%庄志雄
袁建輝%程錦泉%柯躍斌%姬娜娜%週建孟%週麗%黃海燕%楊淋清%劉建軍%徐新雲%莊誌雄
원건휘%정금천%가약빈%희나나%주건맹%주려%황해연%양림청%류건군%서신운%장지웅
乳腺癌耐受蛋白%氟尿嘧啶%乳腺肿瘤%抗药性,肿瘤
乳腺癌耐受蛋白%氟尿嘧啶%乳腺腫瘤%抗藥性,腫瘤
유선암내수단백%불뇨밀정%유선종류%항약성,종류
Breat cancer resistance protein%Fluorouracil%Breast neoplasms%Drug resistance,neoplasm
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(MTr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MrIT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(R2=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.
目的 篩選乳腺癌耐受蛋白(BCRP)介導的耐受藥物,探討BCRP的錶達與耐受藥物的相關性.方法 採用已成功建立的BCRP錶達細胞模型,經細胞存活實驗(MTr法)篩選齣BCRP介導的耐受藥物,併利用高效液相色譜法(HPLC)測定細胞內殘留耐受藥物的相對含量;運用熒光定量逆轉錄.聚閤酶鏈反應(RT-PCR)和免疫組織化學方法(IHC)檢測140例臨床乳腺癌組織標本中BCRP的錶達,同時利用MrIT法研究臨床組織標本對耐受藥物的化學敏感性;採用單項方差統計學檢驗方法分析臨床乳腺癌組織中BCRP的錶達與藥物耐受的相關性.結果 MTT實驗結果顯示,細胞對5.氟尿嘧啶(5-Fu)的耐藥指數隨著BCRP錶達的升高而增加,達到10.58倍(P＜0.05,n=3).HPLC實驗證實BCRP的錶達與細胞內殘留的5-Fu呈顯著的負相關性(r=-0.897,P＜0.05).140例臨床乳腺癌組織標本中,BCRP暘性錶達率為33%(47/140).BCRP暘性錶達的乳腺癌組織對5-Fu的耐藥指數是正常癌徬組織的7-12倍,BCRP的錶達與5-Fu的耐受具有正相關性(R2=0.8124,P＜0.01).結論 BCRP的錶達與5-Fu的藥物耐受具有顯著的相關性,研究結果有助于BCRP暘性;錶達的乳腺癌病人化療方案的製訂和優化.
목적 사선유선암내수단백(BCRP)개도적내수약물,탐토BCRP적표체여내수약물적상관성.방법 채용이성공건립적BCRP표체세포모형,경세포존활실험(MTr법)사선출BCRP개도적내수약물,병이용고효액상색보법(HPLC)측정세포내잔류내수약물적상대함량;운용형광정량역전록.취합매련반응(RT-PCR)화면역조직화학방법(IHC)검측140례림상유선암조직표본중BCRP적표체,동시이용MrIT법연구림상조직표본대내수약물적화학민감성;채용단항방차통계학검험방법분석림상유선암조직중BCRP적표체여약물내수적상관성.결과 MTT실험결과현시,세포대5.불뇨밀정(5-Fu)적내약지수수착BCRP표체적승고이증가,체도10.58배(P＜0.05,n=3).HPLC실험증실BCRP적표체여세포내잔류적5-Fu정현저적부상관성(r=-0.897,P＜0.05).140례림상유선암조직표본중,BCRP양성표체솔위33%(47/140).BCRP양성표체적유선암조직대5-Fu적내약지수시정상암방조직적7-12배,BCRP적표체여5-Fu적내수구유정상관성(R2=0.8124,P＜0.01).결론 BCRP적표체여5-Fu적약물내수구유현저적상관성,연구결과유조우BCRP양성;표체적유선암병인화료방안적제정화우화.
0bjectlve To screen breast cancer resistance protein BCRP-mediated resistance agents and to investigate the relations between BCRP expression and drug resistance. Methods MTY 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 dosageof 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 clinical breast cancer tissue of BCRP expression and drug resistance. Resuits MTF assay showed that increasing resistance of 5-fluorouracil(5-Fu)climbed with the increases of山e 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 doseof 5.Fu with different expression of BCRP(r=一0.897,P<0.05,n=3).F10ny-seven tissue specimens ofBCRP.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 M1Trassay.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.
