POSTSURGICAL ORAL-ADMINISTRATION OF URACIL AND TEGAFUR INHIBITS PROGRESSION OF MICROMETASTASIS OF HUMAN BREAST-CANCER CELLS IN NUDE-MICE

We recently established a metastasis model in nude mice using the MKL- 4 cell line, a contransfectant of the MCF-7 human breast cancer cell l ine with fgf-4 and lacZ in which micrometastases in several organs can be quantitatively observed, First, to develop a new postsurgical meta stasis model, we investigated the timing of occurrence of micrometasta sis and the influence of tumor removal on the progression of micrometa stasis in this model, Micrometastases into lymph nodes and lungs were detected 3 weeks after the cell injections, Tumor removal 3 weeks afte r the injections significantly enhanced the progression of micrometast asis into lymph nodes and bone, Second, to study the effect of a mixed compound, UFT (a molar ratio of uracil: tegafur of 4:1), which has be en widely used in the postsurgical adjuvant setting in Japan, 15 or 20 mg/kg UFT were administered p,o, for 4 weeks to tumor-bearing mice or to mice in which transplanted tumors were resected 3 weeks after the injections, Either dose of UFT significantly inhibited the tumor growt h as well as the progression of micrometastasis into lymph nodes, lung s, liver, and brain, In addition, enhanced progression of micrometasta sis in all explored organs by the tumor removal was significantly inhi bited by the administration of either dose of UFT. In conclusion, this new postsurgical metastasis model may be useful for evaluating the ef ficacy of agents used in the postoperative adjuvant setting, UFT may b e an effective drug for inhibiting the progression of micrometastasis after surgery.