Investigating the Combination therapy effect of Trastuzumab and Idarubicin on growth inhibition of HER2-positive breast cancer cells line (SK-BR-3)

Abstract

Background & Objectives: Trastuzumab and Idarubicin (4-methyl-daunorubicin) are two anti-neoplasmic agents that are widely used in cancer therapy. Idarubicin is more lipophilic than its parent drugs such as daunorubicin, therefore it is absorbed more efficiently by the target cells. The main aim of this study was to Investigate the combinational effect of Trastuzumab (as anti-HER2 monoclonal antibody) and Idarubicin on growth inhibition of HER2 positive breast cancer cells. Material & Methods: In this study, SK-BR-3 cell line as HER2-positive and MCF-7 as cell line with low-level of expression of HER2 were used for treatment process. After 72 hours incubation treatment with various concentrations of indicated agents, induced cytotoxicity of various concentrations of idarubicin, trastuzumab, and idarubicin-trastuzumab as combination was assessed by MTT assay. Results: the results showed that Idarubicin discretely induced similar effect on both cell lines but trastuzumab as it expected induced its effect based on the level of HER2 expression and thus inhibited SK-BR-3 cell line growth in a more potent manner. Between all of treatment methods, idarubicin-trastuzumab therapy was the most efficient and specific treatment for the reduction of cell viability of SK-BR-3 cells as HER2-positive cell line compared to CMF-7 cell line. Indicated combination therapy, reduced viability of SK-BR-3 cells to 17% in comparison with MCF-7 cell line in similar conditions, and induced a significant (p≤0.01) SK-BR-3 cell death compared to MCF-7 cells. Conclusion: It seems that idarubicin combination therapy with trastuzumab in HER2-positive breast cancer cells can be used as an alternative effective treatment.

Keywords

• idarubicin
• trastuzumab (herceptin)
• breast cancer
• combinational therapy
• her2