Single treatment with cisplatin or UFT, but not their combination treatment enhances the metastatic capacity of mouse fibrosarcoma cells

To elucidate the roles of chemotherapeutic agents in tumor progression, we examined whether cis-diamminedichloroplatinum (il) (cisplatin) and UFT woul d promote malignant progression of a weakly tumorigenic and poorly metastat ic fibrosarcoma cell line QR-32SK in vivo. C57BL/6 mice, transplanted with QR32SK, were treated with either cisplatin or UFT alone and in combination. After treatment with or without cisplatin and/or UFT, we established in vi tro culture cell lines from the tumors arising in the mice on day 21 and th en i.v. injected the established cell lines into syngeneic mice, As a resul t, the cell lines established from cisplatin-treated mice and UFT-treated m ice had significantly higher metastatic capacity in lung compared to the on es from control untreated mice (64 and 65%, respectively, versus 26.7%). Th e cell lines established from the mice with the combination therapy showed lower lung metastasis (11%) than the ones from control untreated mice. Furt hermore, we found the incidences of these experimental metastases were clos ely related with in vitro chemotactic activities and the production of MMP- 9 of the cultured cell lines. These results indicate that cisplatin and UFT as a single agent promote the chemotactic activities and the production of MMP-9 in nonmetastatic fibrosarcoma cells, resulting in the conversion to highly metastatic ones, and that cisplatin and UFT in combination failed to promote the chemotactic activities and the conversion. These results sugge st that the combination therapy with cisplatin and UFT is useful in prevent ing the emergence of more malignant tumor cells after chemotherapy. [(C) 19 99 Lippincott Williams & Wilkins.].