Alterations in the Expression Level of mir-1246 and mir-224 in Breast Cancer Cell Lines After Treatment with Taxol Chemotherapeutic Agent

Background & objectives: Breast cancer is one of the most important cancers in women worldwide. Taxol as a chemotherapeutic agent, is used for treatment of breast cancer.The aim of this study was to investigate alterations in the expression of mir-1246 and mir-224 in four breast cancer cell lines after Taxol treatment with the goal of introducing them as a biochemical marker for determining response or resistance of breast cancer to the Taxol therapy. Methods: In this in vitro study, four breast cancer cell lines including MCF-7, MDA-MB-231, SKBR-3 and BT-474 were cultured in RPMI1640 medium supplemented with 10% FBS and antibiotics. Then, MTT assay was performed to determine IC50 concentration of Taxol. Cells were treated for 24 hours and then RNA extraction and cDNA synthesis were performed. Alterations in the expression level of mir-1246 and mir-224 were quantitated using qRT- PCR. Results: After treatment with Taxol, the expression level of mir-1246 was significantly up-regulated in two HER2-overexpressing cell lines, BT-474 (113 fold) and SKBR-3 (1.4 fold), and down-regulated in two HER2-negative cell lines, MCF-7 (45.5 fold) and MDA-MB-231 (7.7 fold). Expression of mir-224 was detected only in two cell lines including SKBR-3 and MDA-MB-231, and was down-regulated after treatment with Taxol (2.1 and 17.2 fold, respectively). Conclusions: According to the different pattern of alteration in the expression level of mir-1246 in HER2-overexpressing breast cancer cell lines compared to HER2-negative cell lines after treatment with Taxol, this miRNA could be a useful biomarker for responsiveness to Taxol in  different types of HER2-positive and -negative breast cancers