Phosphatidylinositol 3-Kinase-Akt Signaling in Pulmonary Carcinoid Cells
Phosphatidylinositol 3-Kinase-Akt Signaling in Pulmonary Carcinoid Cells
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DOI：
10.1016/j.jamcollsurg.2009.03.006
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发表时间：
2009-07-01
影响因子：
5.2
通讯作者：
Kunnimalaiyaan, Muthusamy
中科院分区：
文献类型：
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作者：
Pitt, Susan C.;Chen, Herbert;Kunnimalaiyaan, Muthusamy
背景技术背景：在几种类型的癌症中，磷脂酰肌醇3-激酶（PI 3 K）-Akt信号传导的上调促进肿瘤细胞生长并抑制细胞凋亡。以前的报告表明，该途径促进非小细胞和小细胞肺癌细胞的生长，存活和化疗耐药性。但是PI 3 K-Akt信号通路在肺类癌中的重要性尚未被探讨。在这项研究中，我们的目的是建立PI 3 K-Akt信号转导通路在肺类癌细胞中的作用。研究设计：人肺类癌NCI-H727细胞用LY 294002（0至100 μ M），一个众所周知的PI 3 K抑制剂，或转染Akt 1小干扰RNA（75 nM）。通过3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四唑（MTT）测定法测量细胞增殖长达8天。Western blot分析活化磷酸化Akt（pAkt）、总Akt、Akt 1、神经内分泌标志物嗜铬粒蛋白A（chromogranin A）和无壳-鳞片复合物样蛋白1（achaate-scute complex-like 1）的表达。同样，Akt 1小干扰RNA转染导致肿瘤细胞增殖减少（31.3%）。在PI 3 K抑制和Akt 1 RNA干扰下，均观察到嗜铬粒蛋白A和无毛鳞片样复合物1产生的剂量依赖性降低。Akt 1的表达在所有时间点通过瞬时Akt 1小干扰RNA transfections.CONCLUSIONS：PI 3 K-Akt通路在人肺类癌细胞的肿瘤细胞生长和神经内分泌激素分泌中起作用。抑制Akt 1、PI 3 K-Akt信号或该通路的下游介质可能为肺类癌患者提供治疗方法。（美国科尔外科杂志2009;209：82-88。(C)2009年美国外科医生学会）
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 mu M), 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. (J Am Coll Surg 2009;209:82-88. (C) 2009 by the American College of Surgeons)