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
(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.