Protracted treatment with phorbol ester modulates J-7 human hepatoma-cell-induced aggregation and coagulation of human platelet-rich plasma.
In heparinized human platelet-rich plasma (PRP), J-7 human hepatoma cells initially induced platelet aggregation; then a clot formed. ADP-scavenger systems, apyrase and creatine phosphate/creatine phosphokinase did not inhibit this tumor-cell-induced platelet aggregation (TCIPA), whereas hirudin and concanavalin A completely blocked it. J-7 cells also shortened the recalcification time of normal and of Factor-VIII- and IX-deficient human plasma, although it was inactive in shortening the recalcification time of Factor-VII-deficient plasma. After treatment with phorbol 12,13-dibutyrate (PDBu) for 5 to 90 min, the aggregation and coagulation abilities of J-7 cells were unaffected. Prolonged treatment of J-7 cells with PDBu but not with alpha-PDBu for 24 and 72 hr resulted in gradual loss of aggregation and coagulation. Staurosporine antagonized the effect of PDBu and restored aggregation and coagulation in J-7 cells. Protracted treatment with PDBu (24 or 72 hr) did not affect adherence of J-7 cells to the extracellular-matrix proteins (i.e., fibrinogen, fibronectin, laminin, vitronectin and collagen types I and IV) or to the surface of plastic culture dishes. The treatment also did not affect J-7 cell detachment from plastic culture dishes. These in vitro results demonstrate that protracted phorbol ester treatment diminishes TCIPA and blood coagulation of tumor cells.
Pharmacological Institute, College of Medicine, National Tawian University, Taipei.
F N
FN
Ko
S M
SM
Yu
C M
CM
Teng
D000470:Alkaloids / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000503:physiopathology*; D002448:Cell Adhesion / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005164:Factor IX / Q000502:physiology; D005167:Factor VII / Q000502:physiology; D006493:Heparin / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000503:physiopathology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D019311:Staurosporine; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D016326:Extracellular Matrix Proteins; D006629:Hirudins; D003208:Concanavalin A; D015240:Phorbol 12,13-Dibutyrate; D005167:Factor VII; D005164:Factor IX; D006493:Heparin; D019311:Staurosporine