Hu Ping, He Jingjing, Liu Shiling, Wang Meng, Pan Bingxing, Zhang Wenhua
Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi 330001, P.R. China.
Institute of Life Science, Nanchang University, Nanchang, Jiangxi 330001, P.R. China.
Oncol Rep. 2016 Sep;36(3):1757-63. doi: 10.3892/or.2016.4966. Epub 2016 Jul 22.
Lung cancer is one of the most common cancers worldwide and accounts for 28% of all cancer-related deaths. The expression of the β2‑adrenergic receptor (β2‑AR), one of the stress‑inducible receptors, has been reported to be closely correlated with malignant tumors. However, the role of β2‑AR activation in human lung epithelial‑derived cancer A549 cells and the underlying mechanisms are not fully understood. In the present study, we found that activation of β2‑AR but not β1‑AR promoted the proliferation of A549 cells. Isoproterenol (ISO) stimulation of β2‑AR induced extracellular signal‑regulated kinase 1/2 (ERK1/2) and cyclic adenosine monophosphate response element‑binding protein (CREB) phosphorylation. Blocking the ERK1/2 pathway by U0126 inhibited CREB phosphorylation and also suppressed A549 cell proliferation. Moreover, ISO treatment enhanced the expression of matrix metalloproteinase (MMP) family proteins such as MMP‑2, MMP‑9, and also vascular endothelial growth factor (VEGF), which were able to be blocked by knockdown of CREB. In conclusion, our data revealed that β2‑AR induced ERK1/2 phosphorylation which in turn activated CREB to promote A549 cell proliferation. These findings elucidate potential therapeutic targets for lung cancer treatment.
肺癌是全球最常见的癌症之一，占所有癌症相关死亡人数的28%。据报道，应激诱导受体之一的β2-肾上腺素能受体（β2-AR）的表达与恶性肿瘤密切相关。然而，β2-AR激活在人肺上皮来源的癌细胞A549中的作用及其潜在机制尚未完全明确。在本研究中，我们发现激活β2-AR而非β1-AR可促进A549细胞增殖。异丙肾上腺素（ISO）刺激β2-AR可诱导细胞外信号调节激酶1/2（ERK1/2）和环磷酸腺苷反应元件结合蛋白（CREB）磷酸化。用U0126阻断ERK1/2通路可抑制CREB磷酸化，并抑制A549细胞增殖。此外，ISO处理可增强基质金属蛋白酶（MMP）家族蛋白如MMP-2、MMP-9以及血管内皮生长因子（VEGF）的表达，而敲低CREB可阻断这些蛋白的表达。总之，我们的数据表明β2-AR诱导ERK1/2磷酸化，进而激活CREB以促进A549细胞增殖。这些发现阐明了肺癌治疗的潜在治疗靶点。
