Blockers of adrenergic neurons and receptors, tumor progression and effects of rotational stress in mice.

The aim of this work was to determine the possible participation of adrenergic responses to the increase in tumor dissemination induced by rotational stress using drugs affecting monoaminergic function. The growth of the primary tumor and the formation of lung metastasis were determined in mice implanted with Lewis lung carcinoma, subjected to rotational stress and treated with the adrenergic neuron blocker reserpine, the alpha-receptor blocker phenoxybenzamine, and the beta-blocker propranolol. Treatment with reserpine markedly reduced the formation of spontaneous lung metastasis and completely abolished the increase in metastases caused by rotational stress without direct effect on tumor cells or blood vessels. Phenoxybenzamine and propranolol caused opposite effects on tumor progression. Previous immunosuppression by cyclophosphamide in mice with tumors reduced the antimetastatic effects of reserpine. These results suggesting the importance of the adrenergic modulation of immune resistance factors in controlling metastasis development and indicate a possible role in monitoring the use and effects of monoaminergic drugs in cancer patients.