Intratumor (i.t.) injection of 35 mg/kg/day
NAMI-A for six consecutive days to CBA mice bearing i.m. implants of MCa mammary
carcinoma reduces primary
tumor growth and particularly lung
metastasis formation, causing 60% of animals to be free of macroscopically detectable
metastases. The i.t. treatment allows study of the effects of
NAMI-A on in vivo
tumor cells exposed to millimolar concentrations for a relatively prolonged time. Under these conditions,
NAMI-A reduces the number of CD44+
tumor cells and changes
tumor cell phenotype to a lower aggressive behavior, as shown by scanning electron microscopy analysis. On primary
tumor site,
NAMI-A causes unbalance between 2n and
aneuploid cells in favor of lymphocytes. Furthermore, in
tumor tissue,
nitric oxide production is increased and active
matrix metalloproteinase 9 is decreased, and these effects are accompanied by a reduced
hemoglobin concentration. These data are in agreement with the reduction of
tumor invasion and
metastasis and suggest the therapeutic usefulness of
NAMI-A in neoadjuvant or
tumor reduction treatments for preventing
metastasis formation. These data further stress the usefulness of intratumor treatments as experimental preclinical model for studying in vivo the mechanism of
tumor cell interactions after prolonged exposure to
ruthenium-based compounds to be developed for
metastasis inhibition.