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 activity against a broad range of DNA viruses and is effective against human cytomegalovirus infection.


OBJECTIVE
We aimed to study the effect of cidofovir on growth of the highly 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. In 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-dependent 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 inhibited 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 weekly from the eighth day after the injection of tumour cells, when the tumour 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 the control group it had increased to 750 mm(3).


CONCLUSIONS
Although the mechanism is unknown, an antitumoral or antiangiogenic 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.
Redondo
P
P
Department of Dermatology, University Clinic of Navarra, PO Box 192, 31080 Pamplona, Spain. predondo@unav.es
Idoate
M
M
Galofré
J C
JC
Solano
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000970:Antineoplastic Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir