Abstract
The effects of the treatment of tumor cells of MCa mammary carcinoma and TLX5 lymphoma with the ruthenium complex Na[trans-RuCl4 (DMSO)lm] for several transplant generations were studied on tumor growth and metastases formation. On TLX5 lymphoma cells, treatment was performed in vitro prior to in vivo inoculation of tumor cells in intact or immunesuppressed mice. Either considering tumor take and growth or its capacity to invade the brain of the inoculated hosts, Na[trans-RuCl4(DMSO)lm] did not induce any significant modification. Conversely, in mice with MCa mammary carcinoma, the in vivo treatment of tumor cells in immunesuppressed hosts caused a progressive increase of DNA activity and, starting from the 4th transplant generation, a significantly increased susceptibility of lung metastasis formation to a further treatment in intact mice. These data seem to suggest that Na[trans-RuCl4(DMSO)Im] does not induce chemical xenogenization of tumor cells nor its repeated treatment induces resistance in tumor cells. Conversely, it appears that Na[trans-RuCl4(DMSO)lm] may select a tumor cell population which maintains its capacity to metastasise to the lung but with enhanced sensitivity to the antimetastatic properties of this compound.
Highlights
The effects of a new generation ruthenium(Ill) complex, Na[trans-RuCl4(DMSO)lm], are different from those of cisplatin in that, unlike cisplatin that is active on primary tumor growth and lung colonies, Na[trans-RuCl4(DMSO)lm] is markedly effective only on spontaneous metastases [1,2,3]
The examination of the effects of Na[trans-RuCl(DMSO)lm] on the growth of Mca mammary carcinoma showed a reproducible selective antimetastatic effect prevailing over the effect on the growth of primary tumors
TLX5 lyrnphoma, already shown to be a tumor line poorly responding to Na[trans-RuCl(DMSO)lm], was used because it offers good possibilities to highlight the occurrence of a chemical xenogenization similar to that described by the group of Fioretti [8,9]
Summary
The effects of a new generation ruthenium(Ill) complex, Na[trans-RuCl4(DMSO)lm], are different from those of cisplatin in that, unlike cisplatin that is active on primary tumor growth and lung colonies, Na[trans-RuCl4(DMSO)lm] is markedly effective only on spontaneous metastases [1,2,3]. The selectivity of Na[trans-RuCl4(DMSO)lm] on lung metastases is marked on advanced metastases and accounts for a significant prolongation of host’s survival time, in the experiments in which drug treatment is associated with surgical removal of primary tumor. Either by means of vivo-vivo bioassays or by microscopical examination it appears that the growth of lung tumors is markedly reduced whereas the growth of the i.m. primary tumor is much less affected and histologically not detectable These effects account for the prolongation of the survival time and for the cure rate observed and highlight the pharmacological properties of this compound for the control of solid tumor metastases, an effect that was shown to be exerted on advanced tumor metastases [4,5].
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