INVESTIGADORES
URTREGER Alejandro Jorge
congresos y reuniones científicas
Título:
Effect of Norcantharidine treatment on triple negative mammary tumors progression
Autor/es:
LIZETH ARIZA BAREÑO; AGOSTINA CAMMARATA; DAMIAN DELBART; MARIA J. COSTA; AGUSTINA TARUSELLI; ANDRES BECHIS; LAURA B. TODARO; ALEJANDRO J. URTREGER
Lugar:
Mar del Plata
Reunión:
Congreso; LXIII Reunión Científica de la Sociedad Argentina de Investigación Clínica (SAIC); 2018
Institución organizadora:
Sociedad Argentina de Investigación Clínica (SAIC)
Resumen:
Triple negative breast tumors (TNBC) are a subgroup of breast cancer that do not express estrogen or progesterone receptors and neither overexpress the HER2 receptor. These tumors present a very aggressive clinical course with high rate of recurrence and metastasis incidence.It was previously described that Norcantaridine (NCTD) can inhibit the progression of several cancer types including lung and liver. However, the effect on breast cancer has not been studied yet. Here we analyzed the effect of NCTD in in vitro and in vivo processes associated with malignant progression and metastatic capacity, using human (HS578T) and murine (4T1) TNBC cell lines.NCTD exhibited an important antiproliferative effect, with an Inhibitory Concentration 50 (IC50) of 35uM for 4T1 and 56uM for HS578T cell lines, obtained by MTS assay. By flow cytometry we have demonstrated an increase in the Sub-G0 cell cycle fraction, compatible with the presence of apoptotic cells. Next, we studied the effect of NCTD on adhesion, migration (wound healing), and metalloproteinases (MMPs) secretion (zymography). Moreover, we performed an in vivo lung colonization assay using the 4T1 murine model, syngeneic in BALB/c mice.In both cell lines, NCTD significantly reduced adhesive and migratory capacities also displaying a significant reduction in MMP-9 secreted activity. Although all these parameters could have a direct implication in the malignant progression impairment, in vivo assays showed the pretreatment of 4T1 cells with NCTD induces an increase in the number of lung metastatic nodes.Even though some results obtained are encouraging, we must seek the appropriated therapeutic strategy that allow the safe and effective use of NCTD for the treatment of triple negative breast cancer either as a single drug or in combination with existing therapies.