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Exosomes Serve as Nanoparticles to Deliver Anti-miR-214 to Reverse Chemoresistance to Cisplatin in Gastric Cancer

Wang, Xinyi, Zhang, Haiyang, Bai, Ming, Ning, Tao, Ge, Shaohua, Deng, Ting, Liu, Rui, Zhang, Le, Ying, Guoguang, Ba, Yi·2018·Molecular Therapy
DOI 10.1016/j.ymthe.2018.01.001
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Abstract

Chemoresistance is one of the causes of adverse effects in gastric cancer, including a poor response to cisplatin (DDP). Exosomes loaded with microRNA (miRNA), mRNA, and other non-coding RNAs could regulate drug resistance. Exo-anti-214 was extracted and verified. A Cell Counting Kit-8 (CCK-8) cell viability assay, flow cytometry, and transwell and immunofluorescence assays were performed to determine whether exo-anti-214 could sensitize cells to DDP in vitro. A combination of intravenously injected exo-anti-214 and intraperitoneal DDP was utilized in vivo. Additionally, potential targets of miR-214 were screened by mass spectrometry (MS) and confirmed via western blotting (WB). The levels of miR-214 in the human immortalized gastric epithelial cell line ges-1 and the human gastric adenocarcinoma cell lines SGC7901 and SGC7901/DDP gradually increased. Exo-anti-214 could fuse with cells and regulate potential targets, reducing cell viability, suppressing migration, and promoting apoptosis in vitro. Caudally injected exo-anti-214 was applied to reverse chemoresistance and repress tumor growth in vivo due to the downregulation of miR-214 and overexpression of possible target proteins in tumors. Exo-anti-214 could reverse the resistance to DDP in gastric cancer, which might serve as a potential alternative for the treatment of cisplatin-refractory gastric cancer in the future.

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Metadata

Authors
Wang, X., Zhang, H., Bai, M., Ning, T., Ge, S., Deng, T., Liu, R., Zhang, L., Ying, G., & Ba, Y.
Venue
Molecular Therapy
Publisher
Elsevier BV
Published
2018-03
Volume
26
Issue
3
Pages
774-783
ISSN
1525-0016
DOI
10.1016/j.ymthe.2018.01.001
Cited by
192
References
2
Language
en
Licence
Funders
  • National Natural Science Foundation of China (81602158, 81602156, 81702437, 81702431, 81772629, 81772843)
  • Tianjin Health and Family Planning Commission Foundation of Science and Technology (15KG142)
  • Nature Science Foundation of Tianjin City (16PTSYJC00170)

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