Asara, Yolande (2013) Effetti del Cadmio e del 5 Fluorouracile su cellule di tumore mammario MCF7: analisi morfostrutturale, di espressione genica e proteica. Doctoral Thesis.
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Cadmium (Cd) is considerate one of the most dangerous metals, for men’s health. 5-Fluorouracil (5-Fu) is an antimetabolite used in chemotherapy protocols for solid tumors. The MCF7 human breast cancer cell had been used as cellular model. We analysed the correlation between MCF-7 ultrastructural alterations, Actin and Tubulin cytoskeleton proteins and gene and protein expressions.
MCF-7 were treated with Cd(5μM, 20μM, 40μM) and 5-FU(1.5μM), for 24h and 48h, for TEM, SEM and Immunofluorescence. For gene and protein expression MCF-7 were treated with the Ic 50 (Cd 3μM, and 5-FU 1.5μM) for 6h, 24h, 48h. Gene expression of Bcl2, P53, Bax, Caspase8, Caspase 9, C-Myc, Cyclin A1, Cyclin D1, was studied with qRT-PCR, proteins were analyzed with Western Blot.
In cells Cd treated we observed an intense metabolic activity with alterated mitochondria and alterations in Actin distribution while Tubulin branched out in the cytoplasm. 5-FU-treated cells showed cytotoxicity signs with the presence of pore-like in the membrane cell and degeneration of cytoplasm and nuclei. The addition of 5-FU to the cells Cd treated did not induce significant changes in comparison with the cells Cd treated.
Genes and proteins expressions were significant at 24h. 5-FU+Cd treated cells, had an increase of anti-apoptotic expression of Bcl-2, Cyclins and C-Myc.
Our results suggest that Cd has the ability to stop the cytotoxic effects of 5-FU, used in our experiments and in traditional breast cancer therapy.
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