Phosphatidylinositol 3-kinase-Akt signaling in pulmonary carcinoid cells

Susan C Pitt, Herbert Chen, Muthusamy Kunnimalaiyaan
Journal of the American College of Surgeons 2009, 209 (1): 82-8

BACKGROUND: In several types of cancer, upregulation of phosphatidylinositol 3-kinase (PI3K)-Akt signaling facilitates tumor cell growth and inhibits apoptosis. Previous reports demonstrated that this pathway promotes growth, survival, and chemotherapy resistance in non-small cell and small cell lung cancer cells. But the importance of PI3K-Akt signaling has not been explored in pulmonary carcinoids. In this study, our objective was to establish the role of the PI3K-Akt signal transduction pathway in pulmonary carcinoid cells.

STUDY DESIGN: Human pulmonary carcinoid NCI-H727 cells were treated with LY294002 (0 to 100 microM), a well-known PI3K inhibitor, or transfected with Akt1 small interfering RNA (75 nM). Cellular proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for up to 8 days. Western blot analysis was performed for expression of active, phosphorylated Akt (pAkt), total Akt, Akt1, and the neuroendocrine markers chromogranin A and achaete-scute complex-like1.

RESULTS: Treatment of NCI-H727 cells with LY294002 significantly reduced tumor cell growth (85.3%). Similarly, Akt1 small interfering RNA transfection led to diminished tumor cell proliferation (31.3%). A dose-dependent decrease in chromogranin A and achaete-scute complex-like1 production was observed with both PI3K inhibition and Akt1 RNA interference. Expression of Akt1 was reduced at all time points by transient Akt1 small interfering RNA transfection.

CONCLUSIONS: The PI3K-Akt pathway plays a role in both tumor cell growth and neuroendocrine hormone secretion in human pulmonary carcinoid cells. Inhibition of Akt1, PI3K-Akt signaling, or a downstream mediator of this pathway may provide therapeutic approaches for patients with pulmonary carcinoid tumors.

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