JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Abstract
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.