Inhibition of pulmonary tumor seeding by antiplatelet and fibrinolytic therapy in an animal experimental model.
Fibrin and platelets contribute to the development of blood borne metastases by facilitating the arrest of tumor cell emboli in the microcirculation. We have previously demonstrated that the fibrinolytic agent streptokinase inhibits pulmonary tumor cell seeding in an animal model. To determine whether this effect was potentiated by antiplatelet therapy, a further study was performed to assess the effect of streptokinase in combination with aspirin in a similar model. The results demonstrated that aspirin did not significantly enhance the antimetastatic effect of streptokinase (median: streptokinase = 60, streptokinase + aspirin = 60.5, P = 0.79, Mann Whitney). In a second series of experiments, the antimetastatic effect of streptokinase was compared with another fibrinolytic agent, human recombinant tissue plasminogen activator (rt-PA). Fibrinolytic doses of streptokinase (30,000 units/kg) and rt-PA (5 mg/kg) significantly reduced pulmonary tumor seeding when compared with controls (median: control = 48, streptokinase = 23, P < 0.01, rt-PA = 29, P < 0.001). There was no significant difference in pulmonary tumor seeding between the groups treated with streptokinase and rt-PA (P = 0.56). The clinical implications of these findings are discussed.
Brown
D C
DC
University Department of Surgery, Western Infirmary, Scotland, United Kingdom.
Purushotham
A D
AD
George
W D
WD
D000818:Animals; D001241:Aspirin / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D008175:Lung Neoplasms / Q000473:pathology*; D009366:Neoplasm Seeding; D009360:Neoplastic Cells, Circulating / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D013300:Streptokinase / Q000627:therapeutic use*; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D013300:Streptokinase; D010959:Tissue Plasminogen Activator; D001241:Aspirin