An experimental study of the efficacy of platelet aggregating inhibitor on hepatic metastasis

: To investigate whether OKY-046 (an inhibitor of thromboxane A2 synthetase) and TCV-309 (an antagonist of platelet activating factor) can inhibit VX-2 tumor metastasis, the following studies were performed. Study 1 animal experiment: VX-2 tumors were inoculated and OKY-046 or TCV-309 was administered into the portal vein with or without combination of adriamycin (ADR). The number of tumor nodules on the whole liver surface were counted at three weeks after tumor cells inoculation. The combination of OKY-046 and ADR significantly reduced the number of tumor nodules compared to control and TCV-309. Study 2 in vitro experiment: Human breast cancer cells (MCF-7) overlayed confluently cultured human endothelial cells (HUVEC) in vitro with or without OKY-046 and TCV-309 for 3 days; MCF-7 cells invaded the endothelial cells and built-up colonies. The number of colonies built up were counted. OKY-046 significantly decreased the number of colony formations, but TCV-309 did not. These results suggest that OKY-046 has an inhibitory effect on extravasation of tumor cells.