It has been reported that anticancer drugs at high concentration increase experimental hematogenous metastasis owing to endothelial injury. In this study, we evaluate the effects of anticancer drugs at clinical doses on endothelial cells in the process of metastasis. To do so, we have developed in vitro assay methods which can assess endothelial cell retraction and barrier function against invasion by tumor cells. 5-FU at clinical doses caused neither retraction nor decreasing barrier function, however, ADR and MMC caused retraction of endothelial cells and increased invasion by tumor cells. These effects reached maximum 12 hours after treatment with ADR or MMC, and the number of liver metastases was also significantly increased in in vivo study when tumor cells were injected via portal vein at 12 hours after administration of ADR. It was suggested that some kinds of anticancer drugs at the clinical dose may increase hematogenous metastasis in treatments.
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