The in vivo and in vitro role of nitric oxide in tumor pancreatic growth.

N. MOHAMAD, F. GENRE, L. SAMBUCO, A. GUTIÉRREZ, E. RIVERA, R. BERGOC, G. CRICCO, G. MARTÍN.

Rosario, Argentina.

Congreso; XLII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2006

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

The role of free radical nitric oxide (NO) in tumor biology is controversial but it has been demonstrated that exerts an antiproliferative action in certain tumoral cells. The aim of this work was to assess the NO involvement in the in vivo and in vitro growth of the human pancreatic carcinoma cell line PANC-1. Cell proliferation was evaluated by the clonogenic assay. A dose-dependent inhibition on cell growth was observed when cell cultures were treated with NO synthase (NOS) inhibitors (L-NAME and Aminoguanidine, AG) and the NO donnor (SIN-1). Endothelial and inducible NOS (eNOS and iNOS) isoforms mRNA expression was determined by RT-PCR. eNOS expression was only detected, being positively modulated by L-NAME and negatively by SIN-1. A significant augmentation of intracellular NO level was demonstrated by flow cytometry after L-NAME exposure.Nude mice were sc inoculated with PANC-1 cells. The developed xenografts were undifferentiated adenocarcinomas. When tumour volume reached 65 mm3, animals were divided in two groups: control and AG ( po 2 mg/ml daily in drinking water). AG group showed a lower growth rate, PCNA and antioxidant enzymes SODs, GPx and Cat expression. In conclusion, NO levels modulate in vitro eNOS expression and cell growth. Moreover, free radical NO toxicity and the decrease of the antioxidant enzymes may be involved in the in vivo diminished tumor growth. POSTER