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- Title
Effect of the Combined Administration of mTOR Inhibitor and Dopamine or Somatostatin Analogues in a Human Bronchial Neuroendocrine Cell Line.
- Authors
Pivonello, R.; Sarnataro, M.; Cariati, F.; Pivonello, C.; Colao, A.
- Abstract
Introduction: The mTOR inhibitor rapamycin (RAP) has been considered an anticancer agent. The role of dopamine and somatostatin in controlling cell secretion and proliferation in neuroendocrine tumors (NETs) is still unclear. Aim(s): To: 1) evaluate the expression of dopamine D2 receptor (D2R) and somatostatin SSTR2 receptor in the human bronchial carcinoid cell line NCIH727, and 2) test the effect of RAP, somatostatin analogues (SSA) and dopamine agonists (DA) on vitality, hormone secretion and downstream pathway in H727 cell line. Materials and methods: D2R and SSTR2 expression was demonstrated by western blot (WB) and immunofluorescence. Proliferation was tested by MTT whereas Chromogranin A (CgA) secretion by ELISA to test the effect of RAP, cabergoline (CAB) and octreotide (OCT) alone or in combination. The effect of drugs on cell signaling was assessed by WB. Results: RAP significantly reduced cell viability (20%) and CgA secretion (30%) in a dose-dependent manner. Combined treatment with OCT and CAB had slight additional effect on cell viability and hormone secretion. RAP induced activation and increased phosphorylation of Akt and ERK1/2 which were slightly increased with the combined administration with CAB or OCT. Conclusion: In H727 NET cell line, the growth was significantly inhibited by RAP, whereas OCT and CAB had limited additional antiproliferative and antisecretory effects compared with RAR
- Publication
Neuroendocrinology, 2012, Vol 96, p12
- ISSN
0028-3835
- Publication type
Academic Journal