| 乳腺癌耐受蛋白介导5-氟脲嘧啶的耐受及机制探讨 |
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| 引用本文： | 袁建辉,贺智敏,吕辉,余艳辉,陈主初.乳腺癌耐受蛋白介导5-氟脲嘧啶的耐受及机制探讨[J].深圳特区科技,2005(Z1):106-112. |
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| 作者姓名： | 袁建辉 贺智敏 吕辉 余艳辉 陈主初 |
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| 作者单位： | 1. 深圳市疾病预防控制中心,广东,深圳,518020
2. 中南大学肿瘤研究所,湖南,长沙,410078 |
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| 摘 要： |
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Breast Cancer Resistance Protein Mediates 5-Fluorouracil Resistance and Its Mechanism |
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| Authors: | Yuan Jianhui He Zhimin Lü Hui Yu Yanhui Chen Zhuchu |
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| Abstract: | AIM To filtrate breast cancer resistance protein(BCRP)-mediated resistance agents and investigate the mechanism,so as to provide valuable datum for optimization clinical chemotherapy scheme to tumor with evaluation marker of BCRP expression. METHODS MTT assay was used to filtrate BCRP-mediated resistance agents with PA317/Tet-on/TRE-BCRP cell of different expression levels of BCRP after treated with different concentration anticancer agents. High performance liquid chromatography(HPLC) was applied to measure relative dose of intracellular retention resistance agents. Nuclear DNA fluorescence dye,Hochest 33258, staining and flow cytometry were adopted to detect apoptotic cells after treated with drugs. RESULTS There were shown increasing durg-resistance to 5-fluorouracil,methotrexate, doxirubicin, pirarubicin,etoposide and mitoxantrone followed with increasing expression of BCRP on PA317/Tet-on/TRE-BCRP cells(P＜0.05, n=3),but shown sensitive to paclitaxel, cisplatin, vincristine, mitomycin and vindesine. There also was shown significant negative correlation between the intracellular retention dose of 5-fluorouracil with different expression of BCRP(r=-0.885, P＜0.05, n=3).There were shown parallel results of that decreasing cellular apoptotic rate with increasing cellular expression of BCRP after treated with 5-fluorouracil by fluorescence dye staining and flow cytometry(P＜0.05, n=3),and also shown significate rise of the apoptotic rate of BCRP expression cells after treated with Ko143 (P＜0.05, n=3). Every group of cells could be different extently blocked in phase of G0/G1 treated with 5-fluorouracil. CONCLUSION Resistance of 5-fluorouracil could be especially mediated by conjugated with BCRP and acted as drug exclude-pump substrate. Cellular ability resistant to 5-fluorouracil-induced apoptosis could be reinforced by BCRP expression. |
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| Keywords: | breast cancer resistance protein drug resistance 5-fluorouracil apoptosis anticancer drugs |
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