Anti-cancer effects of the combined treatment of trastuzumab and decoy oligodeoxynucleotides to target STAT3 transcription factor on SK-BR-3 breast cancer cell line

Introduction: Breast cancer is the most common malignancy in the female population and is the leading cause of death. Surgery, chemotherapy, radiotherapy, and monoclonal antibody (trastuzumab) therapy are common and standard treatments for this cancer. However, there are significant limitations in the treatment of this disease by using regular methods. Given the role of transcription factors (TFs) in gene expression, differentiation therapy, and many cancer signaling pathways, in the present study, the effect of combined treatment of trastuzumab (Herceptin) and decoy oligodeoxynucleotides to target the STAT3 transcription factor on inhibition of HER2 positive SK-BR-3 cell line growth was investigated. Materials and Methods: At first, different concentrations of Trastuzumab were prepared from 0.1 to 100 μg/mL. In this way, the decoy and scramble oligodeoxynucleotides were designed and synthesized to target the STAT3 transcription factor. The transfection efficiency and combined effects of trastuzumab with decoy oligos on cell viability, apoptosis, and cell migration inhibition were evaluated. Results: The results showed that oligodeoxynucleotides labeled with Cy3 fluorophore (300 nM) enter the cells with high efficiency (81.7±6.9%). Combined treatment of cells by trastuzumab (10 μg/mL) along with decoy oligodeoxynucleotides (100 nM) led to a decrease in cell viability (58.86±2.71%), increased apoptosis (24.54±4.83%) and inhibited cell migration (45.95±4.21%). Conclusion: The results from this study showed the anticancer effects of combination therapy using trastuzumab with decoy oligodeoxynucleotides to target the STAT3 transcription factor in SK-BR-3 cells. Therefore, it seems that this strategy can be used as an adjunct to common treatments for breast cancer.