Dissociation between thromboxane generation and metastatic potential in cells from a murine fibrosarcoma. Studies with a selective thromboxane synthase inhibitor.
Since the highly metastatic variant M4 of the mFS6 fibrosarcoma has the peculiar feature of generating larger amounts of immunoreactive thromboxane B2 (TxB2) than the non-metastatic variant (M9), we used the thromboxane synthase inhibitor dazmegrel (UK-38,485) in an effort to influence its metastatic potential. TxB2 formation by tumor cells freshly harvested from the primary tumor could be completely inhibited by drug addition in vitro. TxB2 generation was inhibited with a dose-response curve, 2 microM being the lowest dazmegrel concentration giving 100% inhibition. Chronic treatment of tumor-bearing mice with dazmegrel (150 mg/kg b.w. twice daily by gavage) from the day of tumor-cell implantation until killing of the animals caused a more than 10-fold reduction in serum TxB2 formation; TxB2 generation by tumor cells was also significantly depressed. This treatment, however, did not significantly modify either primary tumor weight or metastasis formation. Our data suggest that selective inhibition of thromboxane generation in either blood or tumor cells does not prevent spontaneous metastasis formation in the murine model studied.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D005354:Fibrosarcoma / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013931:Thromboxanes / Q000096:biosynthesis*
D013931:Thromboxanes; D015121:6-Ketoprostaglandin F1 alpha; D013930:Thromboxane-A Synthase