Affiliations: Department of Breast Surgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China
Correspondence:
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Corresponding author: Wen-Hai Zhang, Department of Breast Surgery, Shengjing Hospital, China Medical University, Sanhao Road No.36, Heping District, Shenyang 110004, Liaoning, China. Tel./Fax: +86 024 96615 31511; E-mail:zhangwenhai401@126.com
Abstract: 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.
Keywords: Breast cancer, microRNA-451, neoadjuvant chemotherapy, drug tolerance, circulating serum level, epirubicin-resistant MCF-7 cell line, docetaxel-resistant MCF-7 cell line
