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In this study we have focused on the response of SKBR-3 cells to both single 17-DMAG treatment as well as its combination with photodynamic therapy with hypericin. Low concentrations of 17-DMAG without any effect on survival of SKBR-3 cells significantly reduced metabolic activity, viability and cell number when combined with photodynamic therapy with hypericin. Moreover, IC10 concentation of 17-DMAG resulted in significant increase of SKBR-3 cells in G1 phase of the cell cycle, followed by an increase of cells in G2 phase when combined with photodynamic therapy. Furthermore, 17-DMAG already decreased HER2, Akt, P-Erk1/2 and survivin protein levels in SKBR-3 cells a short time after its application. In this regard, 17-DMAG protected also SKBR-3 cells against both P-Erk1/2 as well as survivin upregulations induced by photodynamic therapy with hypericin. Interestingly, IC10 concentration of 17-DMAG led to total depletion of Akt, P-Erk1/2 proteins and to decrease of survivin level at 48 h. On the other hand, 17-DMAG did not change HER2 relative expression in SKBR-3 cells, but caused a significant decrease of HER2 mRNA in MCF-7 cells characterized by low HER2 expression. These results show that targeting HSP90 client proteins increases the efficiency of antineoplastic effect of photodynamic therapy in vitro.

The present study analyses the effect of flax-seed oil rich in n-3 polyunsaturated fatty acids (PUFAs), the probiotic strain Lactobacillus plantarum -Biocenol TM LP96 and their combination on the expression level of selected Toll-like receptor (TLR) genes (TLR2, TLR4, TLR5, TLR9) and their downstream molecules (myeloid differentiation factor 88, MyD88; nuclear factor-κB, NF-κB) in the jejunum of gnotobiotic pigs challenged with enterotoxigenic Escherichia coli (ETEC). The results show that both immunomodulators are able to modulate the RNA level of at least one of the target molecules and thus regulate pathogeninduced inflammation. We confirmed that not only probiotic lactobacilli or flaxseed oil alone but also their synergistic action has great potential in the prevention and treatment of porcine colibacillosis. The results give an insight into one of the possible mechanisms by which natural agents, such as probiotic lactobacilli and flax-seed oil, exert their immunoregulatory properties during pathogen-induced inflammation.