RESUMO
The BCR-ABL oncogene is a tyrosine kinase gene that is over-expressed in CML. It inhibits the TGF-ß1 signaling pathway. Due to resistance of cells to the tyrosine kinase inhibitor, STI-571, the combined effect of STI-571 and TGF-ß1 on K562 cells was studied in the present research. Results revealed that the TGF-ß1 cell signaling pathway, which is activated in K562 cells treated with TGF-ß1, activates collective cell signaling pathways involved in survival and apoptosis. It is noteworthy that treating K562 cells with STI-571 triggered apoptotic pathways, accompanied by a reduction in proteins such as Bcl-xL, Bcl-2, p-AKT, p-Stat5, p-FOXO3, and Mcl-1 and an increase in the pro-apoptotic proteins PARP cleavage, and p27, leading to an increase in sub-G1 phase-arrested and Annexin-positive cells. Interestingly, the proliferation behavior of TGF-ß1-induced cells was changed with the combination therapy, and STI-571-induced apoptosis was also prompted by this combination. Thus, combination treatment appears to promote sub-G1 cell cycle arrest compared to individually treated cells. Furthermore, it strongly triggered apoptotic signaling. In conclusion, TGF-ß1 did not negatively impact the effect of STI-571, based on positive annexin cells, and AKT protein phosphorylation remains effective in apoptosis.
Assuntos
Proteínas de Fusão bcr-abl , Leucemia Mielogênica Crônica BCR-ABL Positiva , Apoptose , Proteínas de Fusão bcr-abl/genética , Genes abl , Humanos , Mesilato de Imatinib/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Fator de Crescimento Transformador beta1RESUMO
To investigate the effect of 5'-(N-ethylcarboxamido) adenosine (NECA), an adenosine agonist, on triggering angiogenesis in transplanted human ovarian tissue, the expression of angiopoietin-1 (Ang1), Ang2, vascular endothelial growth factor 121 (VEGF-121) and VEGF-189 at both gene and protein levels as well as the density of vasculature were studied in tissue fragments grafted to NECA-treated and control groups of nude mice. The results showed that NECA treatment triggered down-regulation of Ang1, induced VEGF-189 expression, and stimulated neovascularization, highlighting the beneficial effect of NECA on the process of angiogenesis.