Phosphatidylinositol 3-kinase-Akt signaling in pulmonary carcinoid cells.
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.


METHODS
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.
Pitt
Susan C
SC
Endocrine Surgery Research Laboratories, Department of Surgery, University of Wisconsin, Madison, WI 53792, USA.
Chen
Herbert
H
Kunnimalaiyaan
Muthusamy
M
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D002276:Carcinoid Tumor / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D009025:Morpholines / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection
D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one