Effects of DN-9693, a new metastasis inhibitor, on murine hematogenous metastasis

• Published in: Anticancer research Vol. 6; no. 4; p. 543
• Main Authors: Tanaka, N G, Tohgo, A, Ogawa, H, Osada, Y
• Format: Journal Article
• Language: English
• Published: Greece 01.07.1986
• Subjects: 3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors; 3',5'-Cyclic-AMP Phosphodiesterases - pharmacology; Animals; Antineoplastic Agents - pharmacology; Lung Neoplasms - secondary; Male; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Platelet Aggregation - drug effects; Quinazolines - pharmacology; Thromboembolism - prevention & control
• ISSN: 0250-7005

1,5-Dihydro-7-(1-piperidinyl)-imidazo[2,1-b]quinazolin-2(3H)-one dihydrochloride hydrate (DN-9693), a new c-AMP: phosphodiesterase inhibitor was examined for its inhibitory effects on platelet aggregation induced by metastasizing tumor cells and on blood-borne metastases of these tumors. 1-3 microM of DN-9693 completely inhibited platelet aggregation induced by B16 melanoma subline BL6 and Lewis lung carcinoma (3LL) cells. Platelets prepared from mice intravenously or orally administered with DN-9693 failed to aggregate after the addition of BL6 cells. Intravenous injection of DN-9693 was effective in protecting the mice inoculated with 1 X 10(6) BL6 cells against acute pulmonary embolic death. Either intravenous or oral administration of DN-9693 (1-10 mg/kg) sufficiently suppressed thrombus formation and subsequent pulmonary metastasis caused by intravenously inoculated BL6 or 3LL cells. Spontaneous pulmonary metastasis of 3LL was also inhibited by DN-9693. Continuous administration of DN-9693 during and after surgical excision of the primary tumors was the most effective treatment against the development of pulmonary metastases of 3LL.