Evermus, an mTOR Inhibitor, Promotes Apoptosis in Neuroendocrine Tumor Cell BON-1 In Vitro

Abstract

Neuroendocrine tumor derives from neuroendocrine cells, and is commonly occurred in digestive tract, but can be observed in other body sites. The incidence of neuroendocrine tumor is rapidly rising worldwide. Everolimus is a clinically used mTOR inhibitor, and can affect the onset and progression of malignant tumor via suppressing mTOR activity. This study investigated the effect of everolimus on mTOR signal pathway and cell apoptosis of neuroendocrine tumorsin vitro. Human neuroendocrine tumor cell line BON-1 was cultured with different dosages of everolimus. Cell viability was evaluated by MTT assay, and cell apoptosis index was assessed byin situ end labelling of DNA breakage (TUNEL). Western blot was used to compare expressions of mTOR signal pathway related proteins in tumor cells. MTT assay showed that everolimus could dose-dependently inhibit BON-1 cell viability (p < 0 05). TUNEL assay found that apoptotic index of BON-1 cells was elevated by drug treatment (p < 0 05). Western blot found no significant change in mTOR or total Akt protein, but remarkably decrease in p53 and activated caspase-3 proteins (p < 0 05), accompanied with down-regulation of Bcl-2. Everolimus can suppress the viability of neuroendocrine cellin vitro and facilitate apoptosis related protein activity, thus accelerating cell apoptosis.