Abstract:
ObjectiveTo study the effects of exosomal miR-5585-5p derived from paclitaxel-resistant breast cancer cells on the migration, apoptosis and drug resistance of breast cancer cells.
MethodsThe exosomes were obtained by ultracentrifugation, and the expression levels of miR-5585-5p in breast cancer cell line(SKBR-3), paclitaxel-resistant breast cancer cell line(SKBR-3/PR) and exosomes were detected using qRT-PCR.The inhibitor of miR-5585-5p was transfected into paclitaxel-resistant breast cancer cells, the migration ability of cells was detected using Transwell assay, and the apoptosis of cells was detected using flow cytometry.The qRT-PCR and western blotting were used to detect the expression levels of drug-resistant gene.
ResultsCompared with SKBR-3 cell line, the expression levels of miR-5585-5p in drug-resistant SKBR-3/PR cell line and exosomes were up-regulated(P < 0.01 and P < 0.05).After the miR-5585-5p inhibitor was transfected into the drug-resistant cell line, the results of Transwell assay and flow cytometry showed that the drug resistance and biological activity in the inhibitor group decreased compared with the control group(P < 0.01).The co-cultured drug-resistant cell-derived exosomes with breast cancer cells could induce the drug-resistant phenotype, enhance the ability of migration and inhibit the apoptosis rate of SKBR-3 cells(P < 0.01).However, the exosomes derived from drug-resistant breast cancer cells transfected with miR-5585-5p inhibitor could reduce the effects.
ConclusionsThe paclitaxel-resistant breast cancer cells can deliver the highly expressed miR-5585-5p to the parent cells through exosomes, and induce the parent cells to produce drug-resistant phenotypes.The exosome miR-5585-5p can provide new molecular targets for the treatment of breast cancer drug-resistance, and provide new biomarkers for the prognosis assessment of breast cancer.
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