Exosomes mediate drug resistance transfer in MCF-7 breast cancer cells and a probable mechanism is delivery of P-glycoprotein

微泡 MCF-7型 抗药性 流式细胞术 外体 P-糖蛋白 细胞培养 化学 药物输送 癌症研究 癌细胞 癌症 生物 药理学 分子生物学 多重耐药 医学 小RNA 内科学 生物化学 人体乳房 遗传学 有机化学 微生物学 基因
作者
Mengmeng Lv,Xingya Zhu,Wei‐xian Chen,Shanliang Zhong,Qing Hu,Tengfei Ma,Jun Zhang,Lin Chen,Jinhai Tang,Jianhua Zhao
出处
期刊:Tumor Biology [SAGE Publishing]
卷期号:35 (11): 10773-10779 被引量:236
标识
DOI:10.1007/s13277-014-2377-z
摘要

Acquired drug resistance is a major obstacle to chemotherapy of cancers. In this study, we aim to investigate the role of exosomes in drug-resistance transfer between breast cancer cells and detect the probable mechanism. A docetaxel-resistant variant of MCF-7 cell line (MCF-7/DOC) was established and then compared with the drug-sensitive variant (MCF-7/S). Exosomes were expelled from the cell supernatant using ultracentrifugation. Drug resistance was assessed by apoptosis assay and MTT examination. Expressions of P-glycoprotein (P-gp) were analyzed by flow cytometry. Stained exosomes were absorbed by receipt cells. MCF-7/S in the presence of exosomes extracted from the supernatant of MCF-7/DOC (DOC/exo) acquired drug resistance, while MCF-7/S exposed to their own exosomes (S/exo) did not. P-gp expression patterns of exosomes were similar as the originated cells. P-gp expression of MCF-7/S increased after incubation with DOC/exo and was affected by the amount of exosomes. Exosomes are effective in transferring drug resistance as well as P-gp from drug-resistant breast cancer cells to sensitive ones. The delivery of P-gp via exosomes may be a mechanism of exosome-mediated drug resistance transfer.

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