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橙皮苷作为一种预防剂可增强MCF-7乳腺癌细胞系对多柔比星的耐药性。

Hesperidin as a preventive resistance agent in MCF-7 breast cancer cells line resistance to doxorubicin.

作者信息

Febriansah Rifki, Putri Dyaningtyas Dewi Pamungkas, Nurulita Nunuk Aries, Meiyanto Edy, Nugroho Agung Endro

机构信息

Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Yogyakarta, Indonesia ; Pharmacy study programme, Faculty of Medicine and Health Sciences, Universitas Muhammadiyah Yogyakarta, Yogyakarta, Indonesia.

Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Yogyakarta, Indonesia.

出版信息

Asian Pac J Trop Biomed. 2014 Mar;4(3):228-33. doi: 10.1016/S2221-1691(14)60236-7.

DOI:10.1016/S2221-1691(14)60236-7
PMID:25182442
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3868794/
Abstract

OBJECTIVE

To evaluate of hesperidin to overcome resistance of doxorubicin in MCF-7 resistant doxorubicin cells (MCF-7/Dox) in cytotoxicity apoptosis and P-glycoprotein (Pgp) expression in combination with doxorubicin.

METHODS

The cytotoxic properties, 50% inhibition concentration (IC50) and its combination with doxorubicin in MCF-7 cell lines resistant to doxorubicin (MCF-7/Dox) cells were determined using MTT assay. Apoptosis induction was examined by double staining assay using ethidium bromide-acridine orange. Immunocytochemistry assay was performed to determine the level and localization of Pgp.

RESULTS

Single treatment of hesperidin showed cytotoxic activity on MCF-7/Dox cells with IC50 value of 11 µmol/L. Thus, combination treatment from hesperidin and doxorubicin showed addictive and antagonist effect (CI>1.0). Hesperidin did not increase the apoptotic induction, but decreased the Pgp expressions level when combined with doxorubicin in low concentration.

CONCLUSIONS

Hesperidin has cytotoxic effect on MCF-7/Dox cells with IC50 of 11 µmol/L. Hesperidin did not increased the apoptotic induction combined with doxorubicin. Co-chemotherapy application of doxorubicin and hesperidin on MCF-7/Dox cells showed synergism effect through inhibition of Pgp expression.

摘要

目的

评估橙皮苷与阿霉素联合使用时，对阿霉素耐药的MCF-7细胞（MCF-7/Dox）克服阿霉素耐药性、细胞毒性、凋亡及P-糖蛋白（Pgp）表达的影响。

方法

采用MTT法测定橙皮苷在阿霉素耐药的MCF-7细胞系（MCF-7/Dox）中的细胞毒性、50%抑制浓度（IC50）及其与阿霉素联合使用时的情况。通过溴化乙锭-吖啶橙双重染色法检测凋亡诱导情况。采用免疫细胞化学分析法测定Pgp的水平和定位。

结果

橙皮苷单药处理对MCF-7/Dox细胞显示出细胞毒性活性，IC50值为11μmol/L。因此，橙皮苷与阿霉素联合处理显示出相加和拮抗作用（CI>1.0）。橙皮苷与低浓度阿霉素联合使用时，未增加凋亡诱导，但降低了Pgp表达水平。

结论

橙皮苷对MCF-7/Dox细胞具有细胞毒性作用，IC50为11μmol/L。橙皮苷与阿霉素联合使用时未增加凋亡诱导。阿霉素和橙皮苷联合化疗应用于MCF-7/Dox细胞时，通过抑制Pgp表达显示出协同作用。

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