Circulating microRNA-451 as a predictor of resistance to neoadjuvant chemotherapy in breast cancer

• Published in: Cancer biomarkers : section A of Disease markers Vol. 16; no. 3; pp. 395 - 403
• Main Authors: Gu, Xi, Xue, Jin-Qi, Han, Si-Jia, Qian, Song-Ying, Zhang, Wen-Hai
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.01.2016
• Subjects: Antibiotics, Antineoplastic - therapeutic use; Breast Neoplasms - blood; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Cell Line, Tumor; Cell Proliferation - drug effects; Drug Resistance, Neoplasm - genetics; Epirubicin - therapeutic use; Female; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; MicroRNAs - blood; MicroRNAs - genetics; Middle Aged; Neoadjuvant Therapy; Taxoids - therapeutic use; epirubicin-resistant MCF-7 cell line; microRNA-451; neoadjuvant chemotherapy; circulating serum level; docetaxel-resistant MCF-7 cell line; Breast cancer; drug tolerance
• ISSN: 1574-0153; 1875-8592; 1875-8592
• DOI: 10.3233/CBM-160578

OBJECTIVE: We aimed to explore the potential application of circulating microRNA-451 (miR-451) in serum in predicting the resistance to neoadjuvant chemotherapy (NACT) in breast cancer (BC). METHODS: Eighty-two BC patients who underwent NACT were recruited in our study, including 41 NACT-sensitive patients (NACT-sensitive group) and 41 NACT-resistant patients (NACT-resistant group). Additionally, 60 healthy subjects were selected as normal controls. Epirubicin-resistant MCF-7 BC cell line (MCF-7/EPI) and docetaxel-resistant MCF-7 BC cell line(MCF-7/DOC) were cultured in our study. MTT assay was applied to calculate the survival rates of MCF-7 cells, MCF-7/DOC cells and MCF-7/EPI cells. The expression levels of miR-451 in normal controls, NACT-sensitive group, NACT-resistant group, MCF-7 cells, MCF-7/DOC cells and MCF-7/EPI cells were measured by qRT-PCR method. RESULTS: The proliferation rates of both the MCF-7/DOC and MCF-7/EPI cells were significantly restrained at the drug concentration of 10 ng/ml, 50 ng/ml, 100 ng/ml and 200 ng/ml. However, the proliferation rates of MCF-7/DOC and MCF-7/EPI cells both increased significantly at the drug concentration of 500ng/ml. Furthermore, the IC50 of MCF-7/DOC cells was 23.603 ng/ml and the IC50 of MCF-7/EPI cells was 3.209 ng/ml. The relative expression of miR-451 was significantly lower in both the NACT-resistant group and the NACT-sensitive group than the normal control group. We also found that the relative expression level of miR-451 was significantly lower in the NACT-resistant group than that in the NACT-sensitive group. The expression of miR-451 in the MCF-7/EPI and the MCF-7/DOC cell lines was significantly lower than that in the MCF-7 cell lines. CONCLUSION: We supported the view that the relative expression level of miR-451 was lower in the NACT-resistant BC patients, suggesting the circulating miR-451 may have a functional significance in predicting the resistance to NACT in BC patients. We laid a foundation for further research on the resistance to NACT in BC treatment.