title: Interferon alpha and rapamycin inhibit the growth of pheochromocytoma PC12 line in vitro.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: hstep@csk.umed.lodzp.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Motylewska
authors.forename: Hanna
authors.initials: H
authors.lastname: Lawnicka
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kowalewicz-Kulbat
authors.forename: Paulina
authors.initials: P
authors.lastname: Sicinska
authors.forename: Agata
authors.initials: A
authors.lastname: Niedziela
authors.forename: Gabriela
authors.initials: G
authors.lastname: Melen-Mucha
authors.forename: Henryk
authors.initials: H
authors.lastname: Stepien
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D043169:Endostatins / Q000494:pharmacology; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D016716:PC12 Cells; D010673:Pheochromocytoma / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D020123:Sirolimus / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D043169:Endostatins; D007211:Indoles; D016898:Interferon-alpha; C403071:JV 1-36; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; C116890:Semaxinib; D013007:Growth Hormone-Releasing Hormone; D020123:Sirolimus