DX9065A, AN XA INHIBITOR, INHIBITS PROTHROMBIN-INDUCED A549 LUNG ADENOCARCINOMA CELL-PROLIFERATION

In this study we demonstrate that prothrombin activates the cell proli feration of the lung adenocarcinoma A549 cells. The A549 cell expresse s factor Xa-like prothrombinase activity on its surface and prothrombi n was converted to thrombin on the cell surface. Furthermore, thrombin induced the activation of PKC, increased [Ca2+](i) and potentiated MA P kinase activity through thrombin receptor. The mitogenic activity of prothrombin and the conversion to thrombin were completely abolished by the synthetic coagulation factor Xa inhibitor, DX9065a. These findi ngs suggest that DX9065a is an effective agent for a therapeutic strat egy against cancer itself and prothrombotic complications associated w ith malignancy. (C) 1998 Elsevier Science Ireland Ltd.