Cyclosporin A enhances locoregional metastasis of the CC531 rat colon tumour.
The immunosuppressive drug cyclosporin A has been evaluated recently in phase II trials in cancer therapy as a reverter of P-glycoprotein-mediated multidrug resistance. As an immunosuppressive agent, cyclosporin A potentially can enhance tumour growth. We investigated this potency of cyclosporin A in the weakly immunogenic CC531 colon adenocarcinoma model, using the same dose that had previously been shown to intensify the antitumour activity of doxorubicin in vivo. In vitro cyclosporin A caused no growth acceleration and only in high doses was growth inhibition of CC531 cells observed. In vivo no evidence of growth enhancement was found in short-term assays but, after 4 weeks, rats treated with cyclosporin A had a significantly higher tumour load, mainly consisting of locoregional metastases. These experiments in the CC531 tumour model show that cyclosporin A, used as a reverter of multidrug resistance, may produce short-term improvement of antitumour activity but may also induce enhancement of tumour metastasis.
Van de Vrie
W
W
Department of Surgical Oncology, Rotterdam Cancer Institute, The Netherlands.
Marquet
R L
RL
Eggermont
A M
AM
D019813:1,2-Dimethylhydrazine; D000230:Adenocarcinoma / Q000473:pathology / Q000556:secondary*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000473:pathology; D016572:Cyclosporine / Q000009:adverse effects / Q000494:pharmacology*; D004127:Dimethylhydrazines; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D013047:Specific Pathogen-Free Organisms
D000903:Antibiotics, Antineoplastic; D002273:Carcinogens; D004127:Dimethylhydrazines; D007166:Immunosuppressive Agents; D004317:Doxorubicin; D016572:Cyclosporine; D019813:1,2-Dimethylhydrazine