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

Xinyi Wang, Haiyang Zhang, Ming Bai, Tao Ning, Shaohua Ge, Ting Deng, Rui Liu, Le Zhang, Guoguang Ying, Yi Ba

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    35 Scopus citations

    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. Exo-anti-214 could fuse with cells and regulate potential targets, reducing cell viability, suppressing migration, and promoting apoptosis in vitro. Systemically injected exo-anti-214 could reverse chemoresistance and repress tumor growth in vivo because of the downregulation of miR-214 and overexpression of possible target proteins in tumors.

    Original languageEnglish (US)
    Pages (from-to)774-783
    Number of pages10
    JournalMolecular Therapy
    Volume26
    Issue number3
    DOIs
    StatePublished - Mar 7 2018

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    Keywords

    • anti-miR-214
    • chemoresistance
    • cisplatin
    • exosomes
    • gastric cancer

    ASJC Scopus subject areas

    • Molecular Medicine
    • Molecular Biology
    • Genetics
    • Pharmacology
    • Drug Discovery

    Cite this

    Wang, X., Zhang, H., Bai, M., Ning, T., Ge, S., Deng, T., Liu, R., Zhang, L., Ying, G., & Ba, Y. (2018). Exosomes Serve as Nanoparticles to Deliver Anti-miR-214 to Reverse Chemoresistance to Cisplatin in Gastric Cancer. Molecular Therapy, 26(3), 774-783. https://doi.org/10.1016/j.ymthe.2018.01.001