Summary
The effects of a new generation ruthenium(III) complex, Na[trans-RuCl4(DMSO)Im], were compared with the effects of cisplatin in a model of the solid metastasising tumour MCa mammary carcinoma of CBA mice. By examining a number of intraperitoneal and intravenous administration schedules in mice either with spontaneous lung metastases or after artificial induction of tumour colonies, Na[trans-RuCl4(DMSO)Im] was found to behave differently from cisplatin. Unlike cisplatin, which is equally active on primary tumour growth and lung colonies, Na[trans-RuCl4(DMSO)Im] was markedly effective only on spontaneous metastases. The selectivity of Na[trans-RuCl4(DMSO)Im] on lung metastases was also marked on advanced metastases and accounted for a significant prolongation of host survival time, particularly in the experiments in which drug treatment was associated with surgical removal of a primary tumour. In combination with surgery, Na[trans-RuCl4(DMSO)Im] prevented metastasis formation and inhibited the growth of those already formed. This effect, although dependent on the dose used, was not associated with any residual effect on primary tumour cells after treatment discontinuation, whereas it tended to reduce the metastatic ability of the same tumour. This observation stresses the particular propensity of Na[trans-RuCl4(DMSO)Im] to binding metastatic cells rather than other tumour cell clones. On pBR 322 plasmid, Na[trans-RuCl4(DMSO)Im] was as effective as cisplatin in causing termination sites for replication, although it was only weakly active in generating interstrand crosslinking on calf thymus DNA. These data support the view that Na[trans-RuCl4(DMSO)Im] is the first compound capable of selective activity on metastatic tumours, and is therefore capable of showing a significant advantage for the postsurgical prognosis when associated with surgical ablation of primary tumours.
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Sava, G., Pacor, S., Coluccia, M. et al. Response of MCa Mammary Carcinoma to Cisplatin and to Na[trans-RuCl4(DMSO)Im]. Drug Invest 8, 150–161 (1994). https://doi.org/10.1007/BF03259431
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DOI: https://doi.org/10.1007/BF03259431