Lycopene Inhibits Activation of Epidermal Growth Factor Receptor and Expression of Cyclooxygenase-2 in Gastric Cancer Cells
Lycopene Inhibits Activation of Epidermal Growth Factor Receptor and Expression of Cyclooxygenase-2 in Gastric Cancer Cells
复制标题
番茄红素抑制胃癌细胞中表皮生长因子受体的激活及环氧化酶 - 2的表达
DOI：
10.3390/nu11092113
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发表时间：
2019-09-01
期刊：
影响因子：
5.9
通讯作者：
Kim, Hyeyoung
中科院分区：
文献类型：
--
作者：
Han, Hwana;Lim, Joo Weon;Kim, Hyeyoung
活性氧（ROS）作为诱导增殖的信号分子，有助于癌细胞的致癌表型。已知 ROS 可以激活表皮生长因子受体 (EGFR)，从而激活 Ras/丝裂原激活蛋白激酶 (MAPK) 通路。 Ras 依赖性途径促进活化 B 细胞核因子 kappa 轻链增强子 (NF-kappa B) 的激活，NF-kappa B 是环氧合酶 2 (COX-2) 的转录调节剂，可诱导细胞增殖。番茄红素是一种有效的抗氧化剂类胡萝卜素，是水果和蔬菜呈红色的原因。本研究旨在探讨番茄红素是否通过抑制EGFR/Ras/MAPK和NF-kappa B-COX-2信号轴来抑制胃癌AGS细胞的增殖并诱导细胞凋亡。番茄红素降低细胞活力并增加细胞凋亡指数（DNA 碎片、细胞凋亡诱导因子、caspase-3 和 caspase-9 的裂解、Bax/Bcl-2 比率）。番茄红素降低细胞内和线粒体 ROS 水平，并降低 ROS 介导的 EGFR/Ras/细胞外信号调节激酶 (ERK) 和 p38 MAPK 通路的激活，从而导致 NF-kappa B p50/p50 的 DNA 结合活性减弱和 COX-2 基因表达水平。这些结果表明，番茄红素诱导的细胞凋亡和增殖抑制是通过抑制 AGS 细胞中 ROS 激活的 EGFR/Ras/ERK 和 p38 MAPK 通路以及 NF-κ B 介导的 COX-2 基因表达而发生的。总之，食用富含番茄红素的食物可以降低胃癌的发病率。
Reactive oxygen species (ROS) contribute to the oncogenic phenotype of cancer cells by acting as signaling molecules for inducing proliferation. ROS are known to activate the epidermal growth factor receptor (EGFR), which causes the activation of the Ras/mitogen-activated protein kinases (MAPKs) pathway. The Ras-dependent pathway promotes the activation of nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-kappa B), a transcriptional modulator of cyclooxygenase-2 (COX-2) that induces cell proliferation. Lycopene is a potent antioxidant carotenoid and is responsible for the red color of fruits and vegetables. This study aims to investigate whether lycopene inhibits proliferation and induces apoptosis in gastric cancer AGS cells by suppressing the EGFR/Ras/MAPK and NF-kappa B-COX-2 signaling axis. Lycopene decreased cell viability and increased apoptotic indices (DNA fragmentation, apoptosis inducing factor, cleavage of caspase-3 and caspase-9, Bax/Bcl-2 ratio). Lycopene reduced the level of intracellular and mitochondrial ROS and decreased the activation of the ROS-mediated EGFR/Ras/extracellular signal-regulated kinase (ERK) and p38 MAPK pathways, thus leading to attenuation of the DNA-binding activity of NF-kappa B p50/p50 and the level of COX-2 gene expression. These results show that lycopene-induced apoptosis and inhibition of proliferation occur via inhibition of ROS-activated EGFR/Ras/ERK and p38 MAPK pathways and NF-kappa B-mediated COX-2 gene expression in AGS cells. In conclusion, consumption of lycopene-enriched foods could decrease the incidence of gastric cancer.