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激活谷氨酸促代谢型受体8促进肺腺癌A549细胞凋亡

李天娇, 黄艳红, 陈曦, 周舟, 罗四维, 冯丹丹, 汉建忠, 罗自强

中南大学湘雅医学院 1 2011级临床医学专业；生理学；2012级临床医学专业，长沙 410013

摘要

本文旨在检测谷氨酸促代谢型受体(metabotropic glutamate receptors, mGluR)各亚型在肺腺癌A549细胞中的表达，并进一步探讨呈高表达的mGluR8和mGluR4激活对A549细胞体外生长的影响。采用real-time PCR技术检测A549细胞mGluR各亚型的mRNA表达，采用免疫组化技术检测A549细胞以及肺腺癌组织mGluR8和mGluR4蛋白表达。采用CCK-8试剂盒检测细胞生长，EdU掺入检测细胞DNA合成率，hoechst 33258染色及流式细胞仪检测细胞的凋亡的变化，分别观察mGluR8的激动剂(S)-3,4-DCPG及mGluR4的激动剂VU0155041对A549细胞生长的影响。结果显示：A549细胞I组促代谢型受体mGluR1和mGluR5 mRNA呈低水平表达，II组促代谢型受体mGluR2和mGluR3 mRNA无表达，III组促代谢型受体mGluR4、mGluR6、mGluR7和mGluR8 mRNA均有表达，其中以mGluR8的mRNA表达水平最高，mGluR4表达次之；A549细胞及部分患者肺腺癌组织上有mGluR4和mGluR8的蛋白表达。VU0155041对A549细胞的体外生长无明显影响，而(S)-3,4-DCPG呈剂量依赖性抑制A549细胞的生长，并促进其凋亡。这些结果揭示mGluR8激活具有抑制肺癌细胞生长作用，为肺癌防治的研究提供新的线索。

关键词： A549细胞; 谷氨酸促代谢型受体8; 凋亡

分类号：R73-3

[Metabotropic glutamate receptor 8 activation promotes the apoptosis of lung carcinoma A549 cells in vitro.] [Article in Chinese]

LI Tian-Jiao, HUANG Yan-Hong, CHEN Xi, ZHOU Zho, LUO Si-Wei, FENG Dan-Dan, HAN Jian-Zhong, LUO Zi-Qiang

Grade 2011 of Clinical Medicine； Department of Physiology； Grade 2012 of Clinical Medicine, Xiangya School of Medicine, Central South University, Changsha 410013, China

Abstract

This study aims to detect the expression of metabotropic glutamate receptors (mGluRs) in lung carcinoma A549 cells, and to investigate the effects of mGluR8 and mGluR4 activation on the growth of A549 cells in vitro. The mRNA expression levels of the 8 subtypes of mGluRs in A549 cells were determined by real-time PCR. Immunohistochemistry was used to analyze the protein
expression of mGluR4 and mGluR8 in A549 cells and lung tissue sections obtained from lung adenocarcinoma patients. To observe the effects of mGluR8 and mGluR4 activation on the growth of A549 cells, the cultured cells were treated with (S)-3,4-DCPG (an agonist of mGluR8) and VU0155041 (an agonist of mGluR4), respectively, and then the cell viability was analyzed by CCK-8 kit, the percentage of DNA synthesis was detected by EdU incorporation, and the apoptosis of the cells was measured by hoechst 33258 staining and flow cytometry. The results showed that there were low expressions of mGluR1, mGluR5, mGluR6, mGluR7 mRNA, no expression of mGluR2 and mGluR3 mRNA, and high expressions of mGluR8 and mGluR4 mRNA in A549 cells. Accordingly, there were also mGluR4 and mGluR8 protein expressions in the A549 cells and the lung adenocarcinoma tissue sections. VU0155041 had no effect on the growth of A549 cells, but (S)-3,4-DCPG significantly decreased the cells’ growth in a dose-dependent manner and
increased the apoptosis of the cells. The results revealed a role of mGluR8 in the growth and apoptosis of A549 cells and suggested a potential target for clinical treatment of lung cancer.

Key words: A549; metabotropic glutamate receptors 8; apoptosis

收稿日期：2015-02-06　　录用日期：2015-07-02

通讯作者：罗自强　　E-mail: luozq1962@163.com

引用本文：

李天娇, 黄艳红, 陈曦, 周舟, 罗四维, 冯丹丹, 汉建忠, 罗自强. 激活谷氨酸促代谢型受体8促进肺腺癌A549细胞凋亡[J]. 生理学报 2015; 67 (5): 513-520.

LI Tian-Jiao, HUANG Yan-Hong, CHEN Xi, ZHOU Zho, LUO Si-Wei, FENG Dan-Dan, HAN Jian-Zhong, LUO Zi-Qiang. [Metabotropic glutamate receptor 8 activation promotes the apoptosis of lung carcinoma A549 cells in vitro.] [Article in Chinese]. Acta Physiol Sin 2015; 67 (5): 513-520 (in Chinese with English abstract).