Bronchial Carcinoid Response to mTOR Inhibitors Depends on mTOR Expression Levels.

Introduction: Bronchial carcinoids (BCs), originating from endocrine cells dispersed in the respiratory epithelium, can be divided into typical (TBC) and atypical (ABC). TBC are less aggressive, smaller, and much less likely to metastasize, while ABC are more aggressive and metastasize, roTOR has a central role in regulating cell growth, metabolism, and apoptosis. A differential roTOR activation in BCs has been previously demonstrated, suggesting that mTOR pathway might play a predictive role in patients eligible for mTOR-targeted therapies. Aim(s): To evaluate the effects of roTOR inhibitors on human BCs cell lines. Materials and methods: NCIH720 (ABC) and NCIH727 (TBC) cells were treated with Everolimus or with NVP-BEZ 235, a dual PI3K/mTOR inhibitor. Cell viability, caspase activity and cell cycle progression were evaluated after 72 h. Results: Everolimus inhibits cell viability in both cell lines with more pronounced effects on NCIH720, does not activate apoptosis but determines G1/G0 accumulation. NVPBEZ235 had similar effects to Everolimus in terms of cell viability in NCIH727, but was more potent in NCIH720 cells. Caspase activity was not induced by NVP-BEZ 235 in NCIH727, but was enhanced in NCIH720. Western blot and Q-PCR were performed to assess whether this differential effect is due to variations in roTOR expression in BCs cell lines, mTOR expression is 1.5-fold higher in NCIH720 compared to NCIH727. Conclusion: These data demonstrate that mTOR inhibitors affect BCs cell lines differently depending on mTOR expression. [ABSTRACT FROM AUTHOR]