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

被引:300
作者
Lv, Meng-meng [1 ,3 ]
Zhu, Xing-ya [1 ,2 ]
Chen, Wei-xian [3 ]
Zhong, Shan-liang [4 ]
Hu, Qing [3 ]
Ma, Teng-fei [4 ]
Zhang, Jun [3 ]
Chen, Lin [3 ]
Tang, Jin-hai [3 ]
Zhao, Jian-hua [4 ]
机构
[1] Nanjing Med Univ, Clin Sch Nanjing 1, Nanjing 210029, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Gulou Clin Med Coll, Nanjing, Jiangsu, Peoples R China
[3] Nanjing Med Univ, Affiliated Canc Hosp, Canc Inst Jiangsu Prov, Dept Gen Surg, Nanjing 210009, Jiangsu, Peoples R China
[4] Nanjing Med Univ, Affiliated Canc Hosp, Canc Inst Jiangsu Prov, Ctr Clin Lab, Nanjing 210009, Jiangsu, Peoples R China
关键词
P-glycoprotein; Exosomes; Drug-resistance; Docetaxel; Transfer; Breast cancer; ACQUIRED MULTIDRUG-RESISTANCE; EXTRACELLULAR VESICLES; CLINICAL-RELEVANCE; TUMOR-GROWTH; MICRORNAS; BIOMARKERS; PROTEINS; RNA;
D O I
10.1007/s13277-014-2377-z
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
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.
引用
收藏
页码:10773 / 10779
页数:7
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