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

Abstract

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 (105 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.

onclusions: 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.

(Endokrynol Pol 2013; 64 (5): 368–374)