Interferon alpha and rapamycin inhibit the growth of pheochromocytoma PC12 line in vitro.

INTRODUCTION Pheochromocytomas are benign or malignant neuroendocrine tumours. The unsatisfactory efficacy of the traditional therapeutic methods for patients with metastatic disease results in a continuing search for more effective and targeted agents. Due to the increased vascularisation of these tumours, inhibitors of angiogenesis could be potentially a new group of drugs in pheochromocytoma/paraganglioma therapy. MATERIAL AND METHODS The aim of this study was to evaluate the influence of angiomodulators: VEGF (vascular endothelial growth factor) and five endogenous and exogenous antiangiogenic compounds (endostatin; IFN-alpha [interferon alpha]; rapamycin - mTOR [mammalian target of rapamycin] inhibitor; JV1-36 and SU5416 (semaxinib]) on the growth of rat pheochromocytoma PC12 cell line. RESULTS IFN-alpha (10(5) U/mL) strongly inhibited PC12 growth in a 72 h culture, increasing apoptosis and arresting the cell cycle. Rapamycin in a wide range of concentrations (10(-5) to 10(-8) M) induced a slight inhibitory effect on PC12 viability and decreased cell proliferation at the concentration of 10(-5) M. VEGF, endostatin and JV1-36 did not influence the growth of PC12. CONCLUSIONS The study has shown for the first time that IFN-a inhibited the growth of pheochromocytoma PC12 line and confirmed the inhibitory action of rapamycin on these cells. The results suggest that IFN-alpha and mTOR inhibitors could be potentially effective in the therapy of malignant pheochromocytoma, and encourage further study in this field.