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红霉素逆转人肝癌细胞BEL-7402多药耐药性的研究
引用本文:张春梅,石晓峰. 红霉素逆转人肝癌细胞BEL-7402多药耐药性的研究[J]. 中国药理学通报, 2001, 17(6)
作者姓名:张春梅  石晓峰
作者单位:甘肃省医学科学研究院,兰州,730050
基金项目:甘肃省卫生厅资助项目 ,NoGKC97 0 0 9
摘    要:目的 研究红霉素 (ERY)对BEL 740 2细胞 (人肝癌细胞 )多药耐药性的逆转作用。方法 将BEL 740 2细胞连续培养在含阿霉素 (ADM )的培养液中诱导耐药细胞株BEL 740 2 /ADM ,用cell ELASA法检测细胞膜表面P gp的表达 ,细胞毒试验采用MTT法 ,用荧光分光光度法测定细胞内ADM浓度。结果 BEL 740 2 /ADM细胞表面P gp高度表达 ,除对ADM耐药外 ,对长春新碱 (VCR)和丝裂霉素(MMC)也有不同程度的交叉耐药 ;ERY可增强ADM、VCR、MMC对BEL 740 2 /ADM细胞的增殖抑制作用 ,可增加BEL 740 2 /ADM细胞内ADM的浓度而对细胞膜表面P gp的表达没有影响。结论 ERY通过竞争性地饱和BEL 740 2 /ADM细胞表面P gp通道 ,使细胞内药物外排减少、浓度增加 ,从而发挥对BEL 740 2 /ADM细胞多药耐药性的逆转作用

关 键 词:红霉素  人肝癌细胞株  多药耐药  逆转剂

Reversal of multidrug resistance in human liver cancer cells BEL-7402 by erythromycin
ZHANG Chun Mei,SHI Xiao Feng. Reversal of multidrug resistance in human liver cancer cells BEL-7402 by erythromycin[J]. Chinese Pharmacological Bulletin, 2001, 17(6)
Authors:ZHANG Chun Mei  SHI Xiao Feng
Abstract:AIM To study the reversal effect of erythromycin on multidrug resistance of human liver cancer cells BEL 7402. METHODS Cultivated the parental cells BEL 7402 in the presence of doxorubicin to obtain a multidrug resistant subline designated BEL 7402/ADM. The expression of P glycopro tein in BEL 7402 and BEL 7402/ADM cells was determined by using cell ELASA method. The cytotoxicity of drugs was determined by using MTT assay, and the intracellular concentration of doxorubicin in BEL 7402/ADM was determined using a spectrofluorometer. RESULTS After growing BEL 7402 cells in the presence of ADM for some time, the resulting cells (BEL 7402/ADM) became not only resistant to ADM but cross resistant to VCR and MMC, the P gp on the subline cells' surface was highly expresssed. Erythromycin, which is a lipophilic antibiotic, enhanced the anti tumor functions of ADM, VCR and MMC to BEL 7402/ADM cells and increased the intracellular concentration of ADM with no effect on the expression of the P gp in BEL 7402/ADM cells. CONCLUSUON Erythromycin can significantly reverse the multidrug resistance in BEL 7402/ADM cells, it may do so by saturating the P gp pathway to reduce the efflux of intracellular concentration of the drugs.
Keywords:erythromycin  human liver cancer cells line  multidrug resistance  reversal agent
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