Curcumin-Loaded Liposome Alters Chemosensitivity of Breast Cancer Cells to Adriamycin by Regulating the Expression of MicroRNAs

OBJECTIVE To investigate the effect of curcumin-loaded liposome on the chemosensitivity of breast cancer cells to adriamycin via regulating miRNA pathway， and to study its possible mechanism. METHODS Breast cancer cell line MCF-7/ADR was established in vitro by gradually increasing the concentration of adriamycin from the parent cell line MCF-7. The effect of curcumin-loaded liposome altering chemosensitivity of ADR-resistant MCF-7 human breast cancer (MCF-7/ADR) and the synergistic effect index (CI) of ADR and CUR were observed by MTT assay. Differentially expressed miRNAs and mRNAs were detected using miRNA and mRNA microarray. Candidate genes of dysregulated miRNAs were identified by prediction algorithms based on gene expression profiles. RESULTS The combination use of ADR and curcumin-loaded liposome markedly increased inhibition ratio of MCF-7/ADR cells. The array results showed significant differential expression of miRNA and mRNA among MCF-7/S， MCF-7/ADR and curcumin-treated MCF-7/ADR. There were 67 miRNAs and 323 mRNA were differentially expressed in three cell lines. 20 target genes of each dysregulated miRNA not only predicted by prediction software but also differentially expressed in the microarray were discovered. The expression status of hsa-miR-29b-1-5p， hsa-miR-29b-3p， hsa-miR-6068， hsa-miR-6790-5p，has-miR-4417 and DDIT4， EPAS1， VEGFA， RPS14， DCDC2 was validated using qPCR. The results were basically consistent with the analysis results of miRNA microarray. CONCLUSION Curcumin-loaded liposome can rescue part of adriamycin resistance in breast cancer. An altered miRNA expression pattern is involved in acquiring resistance to ADR and miRNA signaling pathways maybe an important molecular pathway through which curcumin-loaded liposome can change the resistance to ADR in breast cancer MCF-7 cells.