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Pheochromocytoma is a tumor of the adrenal medulla for which surgical resection is the only therapy. Though the Notch1 signaling pathway has been suggested as a target for pheochromocytoma treatment, the effect of Notch1 intracellular domain (NICD) on pheochromocytoma cell growth remains unknown. In the present study, the effect of NICD on pheochromocytoma cell growth was examined, by use of a tetracycline‑inducible system for NICD overexpression in the PC12 pheochromocytoma cell line. Flow cytometry was used to determine the effect of NICD on cell cycle phase distribution and apoptosis in PC12 cells. Protein expression levels of microtubule associated protein 1 light chain 3 B (LC3B), Beclin 1, autophagy‑related (ATG) 5 and ATG7 were examined using western blot analysis. Untreated PC12 cells lack NICD expression, while treatment with doxycycline resulted in a significant NICD overexpression. NICD overexpression promoted cell apoptosis and suppressed cell proliferation via regulating S‑phase arrest. In addition, NICD overexpression stimulated the expression of autophagy‑related proteins LC3B, Beclin 1, ATG5 and ATG7. In conclusion, NICD promoted cell apoptosis, suppressed cell proliferation, and stimulated autophagy‑related protein expression in PC12 cells. The present data indicate that overexpression of NICD may be a promising potential therapy for pheochromocytoma.

NICD inhibits cell proliferation and promotes apoptosis and autophagy in PC12 cells