Researchers use exosomes to deliver antagomirs to reverse chemoresistance in gastric cancer

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.

Researchers from the Tianjin Medical University Cancer Institute extracted and verified Exo-anti-214. 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 Fuses into Cells and Regulates Potential Targets

exosomes

(A) Image of exosomes from HEK293T cell medium through a transmission electron microscope. (B) Marker proteins for exosomes were determined via western blot and assessed by gray analysis. (C) Exosomes stained with PKH26 fused into gastric cancer cells. (D) qRT-PCR was applied to test the expression levels of miR-214 and anti-miR-214 in HEK exosomes. (E) Expression levels of the potential target proteins in SGC7901 and SGC7901/DDP cells were detected by western blot. (F) Gray analysis of (E). *p < 0.05; **p < 0.01; ***p < 0.001. All error bars stand for SE.

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. Mol Ther [Epub ahead of print]. [abstract]

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