Time and dose dependency of the suppression of pulmonary metastases of rat mammary cancer by amiloride.

Time and dose dependency of the suppression of pulmonary metastases of rat mammary cancer by amiloride.

Evans D M; Sloan-Stakleff K; Arvan M; Guyton D P

Clinical & experimental metastasis

1998

1998-05

Amiloride is an inhibitor of urokinase plasminogen activator (uPA), an essential component of the plasminogen/plasmin enzyme system. Inhibition of uPA prevents the conversion of plasminogen to tumor cell surface bound plasmin which is required for initiation of the metastatic process. MATB rat mammary cancer cells were introduced into the jugular venous system of 80 Fisher 344 female rats. Amiloride at high and low dosages was administered in the drinking water at the time of, prior to or several days following the tumor cell inoculation and continued daily for 10 days post inoculation. Control rats were maintained on water alone. The middle lobe of the right lung was examined microscopically for numbers of metastases. Suppression of metastases was significant at high amiloride dosages in all groups, and at low dosage when administered prior to inoculation. We conclude that amiloride suppresses induced metastases of rat mammary cancer, the effect being dose- and time-dependent.

Female; Animals; Rats; Drug Administration Schedule; Antineoplastic Agents/*administration & dosage; Neoplasm Transplantation; Amiloride/*administration & dosage; Lung Neoplasms/pathology/*prevention & control/*secondary; Plasminogen Activators/antagonists & inhibitors; Urokinase-Type Plasminogen Activator/antagonists & inhibitors; Dose-Response Relationship; Drug; Mammary Neoplasms; Experimental/*pathology; Inbred F344

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