IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
A pro-angiogenic factor improves gamma-secretase inhibitor antitumoral effect in ovarian cancer xenografts.
Autor/es:
PAZOS MARIA CAMILA; SEQUEIRA GONZALO; TESONE MARTA; IRUSTA GRISELDA
Lugar:
Chascomús
Reunión:
Congreso; XV Jornadas de la Sociedad Argentina de Biología (SAB); 2014
Resumen:
Notch and PDGF
systems are involved in angiogenic process in physiological and pathological
conditions. Here, we developed tumours in nude mice injecting an epithelial
ovarian tumour cell line. SKOV3 cells (1.106cells in 100 μl)
were inoculated subcutaneously into one flank of 6-10 week-old female nude
mice. When the tumours were palpable, the mice were divided in three groups
that received 1. Control, 2. DAPT (5mg/kg gamma-secretasa inhibitor), and 3.
DAPT+PDGFB (0,1mg/kg). The treatments were administered during four consecutive
days (day 1-4). At day 8, the animals were sacrificed and we determined: a. mice
and tumour weight, b. tumour area, c. pericyte area and d. phosphor-AKT and PCNA (cell proliferation marker). Mice weight
did not change between treatments. Tumour weight significantly decreased when
PDGFB was co-administered with DAPT compared to Control group, but no
differences were found between Control and DAPT treatments. Tumour area decreased
with DAPT but not statistically different respect to Control. Interestingly, the
co-treatment completely abolished the tumour growth, being the difference
highly significant on days 7 and 8 post treatment. Similarly, the
periendothelial area increased with PDGFB and DAPT administration. PCNA levels
were significantly decreased in DAPT+PDGF group, but phosphorylated AKT did not
change between groups. We conclude that PDGFB improves the antitumoral effect
of gamma secretasa inhibitor, in part, recruiting periendothelial cells,
stabilizing tumour vasculture, and thus, allowing the inhibitor to better reach
the tumour and exert its antiproliferative effect.