Background: Bronchial carcinoids (BC) are still orphan of medical therapy. We previously demonstrated that the typical BC human cell line NCI-H727 is sensitive to Everolimus, in terms of cell viability reduction, while the atypical human BC cell line NCI-H720 is not. However, the mechanisms underlying this phenomenon have not been fully clarified.
Aim: The aim of our study is to investigate the mechanisms of resistance to mTOR inhibitors in BC cells.
Methods: Cell cycle protein profiling was performed throughout G0/G1/S phases evaluating important complexes regulated during these transition phases at different cell-cycle times, such as CDK2/Cyclin E, CDK4/CyclinD1 and p27Kip1.
Results: The two human BC cell lines, NCI-720 and NCI-727 cells, showed different levels of cell cycle-regulating proteins during cycle progression. We found that under starvation the resistant cell line (NCI-720 cells) still expressed most of the cell cycle regulating protein, while in the sensitive cell line (NCI-727 cells), proteins as p27, cyclin D1 and E were highly down regulated. In addition we observed that, during cell cycle progression, CyclinE/CDK2 complex seems to be more expressed in resistant NCI-H720 cells as compared to NCI-727 cells. In contrast, CyckinD1/CDK4 is more expressed in the sensitive NCI-H727 cell line, while p27 does not show a different expression pattern during cell cycle progression in the two cell lines.
Conclusion: The pattern of proteins involved in cell cycle regulation is clearly different in the two cell lines, suggesting a possible involvement of these molecules in the mechanism of mTOR inhibitors resistance.