Cyclosporin A enhances locoregional metastasis of the CC531 rat colon tumour

Abstract

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.

The Post-Surgical Inflammatory Response Provokes Enhanced Tumour Recurrence: A Crucial Role for Neutrophils

“…It is conceivable that this immunosuppression promotes tumour growth. We observed earlier that immunosuppression leads to enhanced growth of the tumour used in the current experiments [22]. …”

Tacrolimus enhances transforming growth factor-β1 expression and promotes tumor progression

“…Quantitative assessments of hepatic metastases and investigation of regional spread of colon tumor in experimental models found that cyclosporine enhances tumor metastasis (22,23). To the best of our knowledge, our study is the first to demonstrate that tacrolimus promotes tumor metastasis.…”

Characteristics and Survival Patterns of Solid Organ Transplant Patients Developing De Novo Colon and Rectal Cancer

“…Laboratory studies have demonstrated that cyclosporine A, a potent and common immunosuppressant, enhances tumor proliferation and metastasis of colon cancer in animal models. 16,17 The adenoma to carcinoma pathway of CRC is well established and involves APC gene mutation as an early event. 18 It is not known whether the same molecular mechanisms are involved or accelerated in the presence of immunosuppression drugs.…”