C5a激活Akt1-ERK1/2通路促NSCLC细胞的增殖和迁移
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1.南京医科大学;2.南京医科大学第一附属医院肿瘤科

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C5a induces the proliferation and migration of NSCLC cells through the activation of Akt1-ERK1/2 pathway
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    摘要:

    [摘要] 目的:探讨C5a对非小细胞肺癌(non-small cell lung cancer,NSCLC)细胞增殖和迁移的影响及其潜在的分子机制。方法:RT-PCR和Western blot检测人正常支气管上皮细胞系BEAS-2B和三种NSCLC细胞系 (H1703、PC9、H1299)中C5a受体(C5aR)的表达;CCK-8和划痕实验检查C5a对PC9细胞增殖和迁移的影响;Western blot检查C5a刺激PC9细胞后蛋白激酶Akt1、细胞外信号调节激酶1/2(extracellular signal-regulated kinase,ERK1/2)和蛋白激酶C-α(protein kinase C-α,PKC-α)表达及磷酸化水平;用Akt1抑制剂Perifosine和ERK1/2抑制剂U0126分别处理PC9细胞后再给予C5a刺激,Western blot检查Akt1和ERK1/2的表达和磷酸化及其上下游调控关系,CCK-8和划痕实验检测Perifosine和U0126对细胞增殖和迁移的影响。结果: PC9细胞C5aR的表达水平显著高于其它细胞;C5a可明显促进PC9细胞的增殖和迁移能力;C5a刺激PC9细胞后,可显著增强Akt1和ERK1/2的磷酸化;Akt1和ERK1/2抑制剂均能明显下调C5a刺激PC9细胞后引起的细胞增殖和迁移,且Akt1抑制剂不仅能减弱Akt1的磷酸化,还能减弱ERK1/2的磷酸化,而ERK1/2抑制剂则仅能阻断其自身的磷酸化。结论:C5a刺激NSCLC细胞后可能通过激活Akt1-ERK1/2通路促进细胞增殖和迁移。

    Abstract:

    [Abstract] Objective: To investigate the effect of C5a on the proliferation and migration of non-small cell lung cancer (NSCLC) cells and its potential molecular mechanism. Methods: The C5a receptor (C5aR) expression in the human normal bronchial epithelial cell line BEAS-2B and three NSCLC cell lines (H1703, PC9, H1299) examined by RT-PCR and western blot (WB) analysis; PC9 cell were stimulated with various concentrations of C5a, and cell proliferation and migration by CCK-8 and scratch test; The PC9 cells were treated with C5a, and then the expression and phosphorylation of Akt1, ERK1/2 and PKC-α at different time points by WB; PC9 cells were respectively treated with Akt1 inhibitor (Perifosine) and ERK1/2 inhibitor (U0126) followed by C5a stimulation, WB was used to examine the expression and phosphorylation level of Akt1 and ERK1/2 and their upstream and downstream regulatory relationships. The effected of Perifosine and U0126 on PC9 cells proliferation and migration by CCK-8 and scratch test. Results: The expression level of C5aR in PC9 cells is significantly higher than that of other cells; C5a can significantly promote the proliferation and migration of PC9 cells; The phosphorylation levels of Akt1 and ERK1/2 were all markedly enhanced in the PC9 cells induced by C5a, but the total protein expression did not show significant change; Akt1 and ERK1/2 inhibitors can significantly down-regulate the proliferation and migration caused by C5a stimulation of PC9 cells, and Akt1 inhibitors can not only attenuate the phosphorylation of Akt1, but also attenuate the phosphorylation of ERK1/2, and ERK1/2 inhibits The agent can only attenuate its own phosphorylation. Conclusion:C5a induces the proliferation and migration of NSCLC cells through the activation of Akt1/ERK1/2.

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  • 收稿日期:2021-06-28
  • 最后修改日期:2021-08-06
  • 录用日期:2021-12-23
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