Investigation of the effects of DZNep and stauprimid combination on MYC gene expression in breast cancer

Breast cancer, which is the most prevalent among women in the world, is a heterogeneous and complex disease and this heterogeneity is increasing. There are many subtypes of breast cancer. Early diagnosis and treatment of breast cancer has an important role in the prognosis of the disease. The MYC gene, a key regulator of cell growth, differentiation, apoptosis and proliferation, is also associated with the development and progression of breast cancer. Studies have shown that suppression of MYC gene overexpression has an antiproliferative effect on breast cancer cells. As a therapeutic target, stauprimidine inhibits overexpression of the MYC gene by inhibiting NME / NM23 nucleoside diphosphate kinase 2 (NME2) nuclear localization in embryonic stem cells. DZNep (3-Deazaneplanocin-A) inhibits H3K27me3 methylation in the EZH2 (Enhancer of vine homologous 2) pathway. According to the data we were obtained, doses effects was detected at 72 h for MDA-MB-231 cell line the IC50 doses of Stauprimide 2.74 µM, DZNep 182.75 µM, the combination of agents 1:1 ratio ED50 0,33 µM and CI (combination index) 0.134 strong synergism, for MCF-7 cell line the IC50 doses of Stauprimide 2.07 µM, DZNep 115.0 µM, the combination of agents 1:1 raito ED50 1.37 µM and CI 0.671 synergism, for MCF-10A cell line the IC50 doses of Stauprimide 19.9 µM, DZNep 108.6 µM, the combination of agents 1:1 ratio ED50 7.9 µM and CI 0.470 synergism. In the wound healing experiment, less closing formation were observed in the combination application of the substances compared to the control group and separate agent treatment. The use of DZNep and Stauprimide agents as a combined treatment has been analyzed in flow cytometry, which has a more anti-prolifaretive effect than the use of a single anti-tumor treatment on breast cancer cells. In this context, regulation of MYC gene was achieved. In the context of all these results, the effect of both agents on MYC gene and induction of apoptosis shows that there is synergistic effect between these two agents. Combined therapeutic therapies to be used after in vivo and phase studies are predicted to be beneficial. Keywords; Breast Cancer, EZH2 pathway, NME2 pathway, DZNep, Staurpimde, Polycomb Group (PcG) Proteins