However, overexpression of NME1 and NME2 genes was found only in SH-SY5Y cells after combined treatment
with ATRA and inhibitors. The overexpression of this gene family was reported to be associated with more differentiated phenotypes in human and murine neuroblastoma cell lines [33–35]. Similar changes were observed in the SH-SY5Y cell line and in the expression of the CDKN1A gene after combined treatment with ATRA and both inhibitors; the CDKN1B gene was overexpressed in SH-SY5Y cells with a combination of ATRA and CX only. An increase in the expression of cyclin kinase inhibitors by RA alone and in combination with histone deacetylase inhibitors was Selleck Captisol reported . Moreover, inhibition of cdk activity was repeatedly confirmed to be a determinant of neuronal differentiation . The same expression pattern was found in SH-SY5Y cells and for the NINJ1 gene; this gene encodes adhesion molecules promoting find more neurite outgrowth . RA-induced differentiation of neuroblastoma
cells is also associated with the overexpression of tumor necrosis factor receptors (TNFRs) . In SH-SY5Y cells, we noted JPH203 order an increase in the expression of the TNFRST10B gene after treatment both with 10 μM ATRA alone and with all combinations of ATRA and inhibitors. To summarize, in addition to the genes generally overexpressed in both cell lines after combined treatment, as listed above, we also identified other genes that are specifically influenced in specific cell lines, including SK-N-BE(2) or SH-SY5Y. These genes are also known to be involved in the process of neuronal differentiation in neuroblastoma cells; however, their regulation is obviously cell Metalloexopeptidase type-specific and is independent of the inhibitor type. Nevertheless, we also determined sets of genes influenced specifically
by combined treatment with ATRA and CA in both SK-N-BE(2) and SH-SY5Y cell lines; but changes in the gene expression of such genes may differ between these cell lines. In contrast, the very same increase of AKT1 gene expression in both cell lines treated with the combination of 1 μM ATRA and CA was observed. Published results on SH-SY5Y cells suggest that the PI3K/Akt signaling pathway is activated during RA-induced differentiation . We also identified genes influenced specifically by the combined treatment with ATRA and CX in both SK-N-BE(2) and SH-SY5Y cell lines. The most interesting finding is the overexpression of the HMGA1 gene in both cell lines after combined treatment with ATRA and CX in a concentration-dependent manner. According to published data, retinoic acid may increase HMGA1 expression in RA-resistant neuroblastoma cells, but it inhibits this expression in cells undergoing RA-induced neuronal differentiation .