title: Interferon alpha and rapamycin inhibit the growth of carcinoid and medullary thyroid cancer in vitro.
abstract: Neuroendocrine tumors (NETs) are highly vascularized neoplasms characterized by rising incidence. Moreover, the neuroendocrine cells were shown to express vascular endothelial growth factor (VEGF) and VEGF receptors. Therefore, angiomodulators could be potentially a new group of drugs enhancing still unsatisfactory effectiveness of NET therapy. The aim of this study was to assess the direct influence of angiomodulators: VEGF and five endogenous and exogenous antiangiogenic compounds (endostatin, interferon alpha [IFNα], rapamycin, JV1-36, semaxinib [SU5416]) on the growth of two NET cell lines: lung carcinoid H727 cell line and medullary thyroid cancer TT cell line in vitro. IFNα and rapamycin induced the inhibitory effect on H727 and TT cell viability and proliferation, increasing apoptosis and arresting the cell cycle. Also semaxinib (10(-5)M) inhibited proliferation of both cell lines. VEGF and endostatin did not influence the growth of H727 and TT cells. The inhibitory effect of IFNα, rapamycin and semaxinib on carcinoid and medullary thyroid cancer growth was revealed in our in vitro study, although some other antiangiogenic agents did not directly influence H727 and TT cell growth. Thus, IFNα and mTOR inhibitors as multidirectionally acting drugs with antiangiogenic effect could be potentially efficient in treatment of neuroendocrine tumors and are worth further studies.
authors.affiliation: Department of Immunoendocrinology, Chair of Endocrinology, Medical University of Lodz, Łódź, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Motylewska
authors.affiliation: Department of Immunoendocrinology, Chair of Endocrinology, Medical University of Lodz, Łódź, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Lawnicka
authors.affiliation: Department of Immunology and Infectious Biology, University of Lodz, Łódź, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kowalewicz-Kulbat
authors.affiliation: Department of Environmental Pollution Biophysics, University of Lodz, Łódź, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Sicinska
authors.affiliation: Department of Immunoendocrinology, Chair of Endocrinology, Medical University of Lodz, Łódź, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Niedziela
authors.affiliation: Department of Immunoendocrinology, Chair of Endocrinology, Medical University of Lodz, Łódź, Poland.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Melen-Mucha
authors.affiliation: Department of Immunoendocrinology, Chair of Endocrinology, Medical University of Lodz, Łódź, Poland. Electronic address: hstep@csk.umed.lodz.pl.
authors.forename: Henryk
authors.initials: H
authors.lastname: Stepien
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002116:Calcitonin / Q000378:metabolism; D002276:Carcinoid Tumor / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D018278:Carcinoma, Neuroendocrine; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D020123:Sirolimus / Q000494:pharmacology*; D013964:Thyroid Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D016898:Interferon-alpha; D002116:Calcitonin; D020123:Sirolimus
keywords: Angiogenic factors; H727 line; Interferon alpha; Rapamycin; TT line