Cisplatin-resistant MDA-MB-231 Cell-derived Exosomes Increase the Resistance of Recipient Cells in an Exosomal miR-423-5p-dependent Manner.

摘要: Background Chemoresistance blunts the therapeutic effect of cisplatin (DDP) on Triple-Negative Breast Cancer (TNBC). Researchers have not determined to date whether exosomes confer DDP resistance other breast cancer cells or exosomal transfer miRNAs derived from DDP-resistant TNBC resistance. Objective The aim this study was investigate role in chemoresistance cancer. Methods MDA-MB-231 resistant (231/DDP) were established. Exosomes isolated 231/DDP (DDP/EXO) and characterized by measuring levels protein markers, nanoparticle tracking analysis transmission electron microscopy. MDA-MB-231, MCF-7 SKBR-3 cell lines treated with DDP/EXOs proliferation cytotoxicity evaluated using MTT assays apoptosis analyses. Western blotting used examine P-glycoprotein (P-gp) expression. Additionally, a microarray analyse microRNA (miRNA) expression profiles exosomes. effects RT-PCR. Exosomal miR-423-5p extracted, differential verified. viability assay, flow cytometry, Transwell immunofluorescence performed determine if sensitized vitro. Results Under microscope, exhibited round oval shape diameter ranging between 40 100 nm. labelled PKH67 taken up cells. After an incubation DDP/EXOs, higher IC50 value for cisplatin, P-gp expression, migration invasion capabilities lower rate. Furthermore, 60 significantly up-regulated compared Notably, corresponding sensitive exosomes, miR-370-3p, miR-373 most differentially expressed We chose miR-423-5p, up-regulation down-regulation affected Conclusions altered sensitivity dependent manner. Our research helps elucidate mechanism