INVESTIGADORES
MARTIN Gabriela Adriana
artículos
Título:
Aminoguanidine impedes human pancreatic tumor growth and metastasis development in nude mice.
Autor/es:
MOHAMAD N, CRICCO G, SAMBUCO L, CROCI M, MEDINA V, GUTIÉRREZ A, BERGOC R, RIVERA E, MARTÍN G.
Revista:
WORLD JOURNAL OF GASTROENTEROLOGY
Editorial:
W J G PRESS
Referencias:
Lugar: Beijing; Año: 2009 vol. 15 p. 1065 - 1071
ISSN:
1007-9327
Resumen:
AIM: To study the action of aminoguanidine on
pancreatic cancer xenografts in relation to cell
proliferation, apoptosis, redox status and vascularization.
METHODS: Xenografts of PANC-1 cells were developed
in nude mice. The animals were separated into two
groups: control and aminoguanidine treated. Tumor
growth, survival and appearance of metastases were
determined in vivo in both groups. Tumors were excised
and ex vivo histochemical studies were performed. Cell
growth was assessed by Ki-67 expression. Apoptosis
was studied by intratumoral expression of B cell
lymphoma-2 protein (Bcl-2) family proteins and Terminal
deoxynucleotidyl transferase biotin-dUTP Nick End
Labeling (Tunel). Redox status was evaluated by the
expression of endothelial nitric oxide synthase (eNOS),
catalase, copper-zinc superoxide dismutase (CuZnSOD),
manganese superoxide dismutase (MnSOD) and
glutathione peroxidase (GPx). Finally, vascularization
was determined by Massons trichromic staining, and by
VEGF and CD34 expression.
RESULTS: Tumor volumes after 32 d of treatment by
aminoguanidine (AG) were significantly lower than
in control mice (P < 0.01). Median survival of AG
mice was significantly greater than control animals
(P < 0.01). The appearance of both homolateral and
contralateral palpable metastases was significantly
delayed in AG group. Apoptotic cells, intratumoral
vascularization (trichromic stain) and the expression of
Ki-67, Bax, eNOS, CD34, VEGF, catalase, CuZnSOD and
MnSOD were diminished in AG treated mice (P < 0.01),
while the expression of Bcl-2 and GPx did not change.
CONCLUS ION: T h e a n t i t umo r a l a c t i o n o f
aminoguanidine is associated with decreased cell
proliferation, reduced angiogenesis, and reduced
expression of antioxidant enzymes.