Cidofovir inhibits growth of B16 melanoma cells in vivo

Background Cidofovir [(S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl) cytosine ] is a commercially available nucleotide analogue that has antiviral activi ty against a broad range of DNA viruses and is effective against human cyto megalovirus infection. Objectives We aimed to study the effect of cidofovir on growth of the highl y aggressive melanoma tumour arising from mouse melanoma B16 cells grafted subcutaneously in C57B16/J mice. Methods Mice were treated daily with systemic cidofovir at several doses. I n treated and control groups, tumour growth was measured using a calliper, and histological studies were performed. Results In untreated mice, massive invasive melanoma tumours were observed on day 5 after tumour cell grafting. Cidofovir treatment gave a dose-depend ent reduction in tumour size. Tumour growth was inhibited by 62% at a dose of 37.5 mg kg(-1) three times weekly, as compared with control mice treated with saline alone. At 67 mg kg(-1) three times weekly, tumour growth was i nhibited by 90%. Increasing the cidofovir dose to 50 or 100 mg kg(-1) daily resulted in a gradual increase in the antitumoral effect of the compound. In one experiment, cidofovir was administered at 100 mg kg(-1) five times w eekly from the eighth day after the injection of tumour cells, when the tum our already had a volume of approximately 100 mm(3). In the treatment group , on the 14th day the tumour volume was approximately 200 mm(3), while in t he control group it had increased to 750 mm(3). Conclusions Although the mechanism is unknown, an antitumoral or antiangiog enic effect may be the reason for the activity of cidofovir in this model. In view of our findings, use of cidofovir should be further explored in the treatment of neoplastic diseases.