Effects of thiorphan, bestatin and captopril on the Lewis lung carcinoma metastases in mice.

Previously we have found that administration of thiorphan alone or in combination with bestatin exerts antitumor effect in mice, including reduction of B16 melanoma tumor growth and prolongation of survival time. These data prompted us to extend our studies to estimate the effect of treatment with thiorphan, captopril and bestatin on lung metastases in mice. Administration of thiorphan alone at a dose of 25 micrograms/mouse or in combination with bestatin (50 micrograms) or captopril (5 mg/mouse) decreased the number of spontaneous metastases in lungs of Lewis lung carcinoma bearing mice. Neither the injections of bestatin, captopril nor bestatin in combination with captopril influenced the number of lung tumor colonies. Treatment with thiorphan at a dose 25 micrograms augmented cytotoxic activity of natural killer (NK) cells and macrophages. These observations explain partly the mechanism of action of thiorphan.