Yalovenko T. The role of hepcidin in drug resistance formation to doxorubicin.

The thesis is devoted to the actual issue of oncology - analysis of HEPC content in the context of during formation of drug-resistant phenotype to doxorubicin in BC experimental models in vitro and in vivo and to the grounding of possibilities of using indices of serum and tumor HEPC as the marker of BC sensitivity to neoadjuvant polychemotherapy. In in vitro experimental system higher levels of HEPC were found in MCF-7/Dox cells compared with sensitive MCF-7 cells (p <0.05). In the experimental system in vivo, we have demonstrated that the increase of HEPC in serum (sHEPC) and in tumor tissue (tHEPC) of the experimental animals is an important component of the doxorubicin resistance formation and progression of tumor growth. In the clinical material of BC patients, we have found that increase of sHEPC and tHEPC rates is associated with malignancy processes in the breast. We have established that increased expression of HEPC in tumor tissue and its serum levels in peripheral blood of BC patients are inversely correlated with reduced expression of miR-122 (r = -0.62; r =0 -0.68, respectively; p <0.05). The association of sHEPC and circulating miR-122 with sensitivity to neoadjuvant polychemotherapy of BC patients was proven (p <0.05) suggesting that these indicators may be useful as additional objective markers of the sensitivity of breast cancer to the neoadjuvant chemotherapy regimen.