INHIBITION OF EXPERIMENTAL BLOOD-BORNE LUNG METASTASIS BY PROTEASE INHIBITORS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (7) , 2539-2542
Abstract
The inhibitory effects of protease inhibitors on blood-borne metastasis in male Donryu rat lung were studied. Injection i.v. of 106 [rat] Yoshida ascites hepatoma AH7974 cells induced about 118 .+-. 92 (SD) metastatic foci in rat lung after 3 wk. Leupeptin (50 mg/kg body wt twice a day), injected i.p. from 2 days before to 4 days after the inoculation of tumor cells, reduced the number of metastatic foci to about 49 .+-. 45 (P < 0.005). Leupeptin also suppressed the formation of metastatic foci of Yoshida ascites hepatoma AH100B cells (P < 0.001). Elastatinal (100 mg/kg body wt twice a day) and chymostatin (100 mg/kg body wt once a day) did not inhibit formation of metastatic foci of AH7974 cells. Injection i.v. of 106 AH7974 cells induced pulmonary thrombi within 1 h. Leupeptin (50 mg/kg body wt twice a day) reduced the number of thrombi from 1298 .+-. 395 to 646 .+-. 218, when injected i.p. for 2 days before the inoculation of the cells (P < 0.005). Chymostatin and elastatinal did not significantly change the number of pulmonary thrombi. Leupeptin apparently inhibited metastasis formation. This effect may be due to the inhibition of thrombus formation [through inhibition of thrombokinase activity] after the arrest of circulating tumor cells.