GRM4正向别构调节剂抑制乳腺癌细胞的增殖并促进细胞凋亡

doi:10.19401/j.cnki.1007-3639.2018.08.001

中国癌症杂志 ›› 2018, Vol. 28 ›› Issue (8): 561-566.doi: 10.19401/j.cnki.1007-3639.2018.08.001

GRM4正向别构调节剂抑制乳腺癌细胞的增殖并促进细胞凋亡

李林海¹，肖　斌¹，郭梓璇²，赖斯华³，古丽米热•安外尔³，符玉文¹，陈建芸¹，孙朝晖¹

1. 中国人民解放军广州总医院检验科，广东广州510000 ；
2. 嘉应学院检验系，广东梅州 514000 ；
3. 广州医科大学检验系，广东广州510000

出版日期:2018-08-30 发布日期:2018-09-14
通信作者: 李林海 E-mail: mature303@126.com
基金资助:
2017年度军队后勤科研项目（CWH17C017）；2018年度广州市科技计划项目（201804010186）。

GRM4 positive allosteric modulators inhibit breast cancer cell proliferation and promote cell apoptosis

LI Linhai¹, XIAO Bin¹, GUO Zixuan², LAI Sihua³, GULIMIRE·An Waier³, FU Yuwen¹, CHEN Jianyun¹, SUN Zhaohui¹

1. Department of Clinical Laboratory Midicine, Guangzhou General Hospital of PLA, Guangzhou 510000, Guangdong Province, China; 2. Department of Medical Laboratory, Jiaying University, Meizhou 514000, Guangdong Province, China; 3. Department of Medical Laboratory, Guangzhou Medical University, Guangzhou 510000, Guangdong Province, China

Published:2018-08-30 Online:2018-09-14
Contact: LI Linhai E-mail: mature303@126.com

摘要/Abstract

摘要： 背景与目的：代谢型谷氨酸受体4（glutamate metabotropic receptor 4，GRM4）在多种恶性肿瘤中高表达并与肿瘤患者的预后相关，但GRM4在乳腺癌中的生物学作用仍不清楚。本研究拟探讨GRM4的两种正向别构调节剂VU0364439及VU0364770对乳腺癌细胞的增殖及凋亡的影响，进而为乳腺癌的靶向治疗提供思路。方法：在体外培养的乳腺癌细胞系MDA-MB-231、MCF-7和SK-BR-3中分别单独加入VU0364439、VU0364770以及联合使用两种试剂，利用CellTiter-Glo^®发光细胞活力测定法定量检测各组乳腺癌细胞系的增殖活性；利用Annexin Ⅴ-PI双染法检测各组乳腺癌细胞系的凋亡水平；通过实时荧光定量聚合酶链反应（realtime fluorescent quantitative polymerase chain reaction，RTFQ-PCR）技术测定GRM4基因在6种乳腺癌细胞系中的表达情况，在GRM4表达水平最高的细胞中单独加入或联合使用VU0364439及VU0364770，用RTFQ-PCR检测GRM4基因表达的改变。结果：与对照组相比，单独使用及联合使用VU0364439及VU0364770显著抑制乳腺癌细胞MCF-7、MDA-MB-231和SK-BR-3的增殖水平，并促进MCF-7细胞凋亡现象的发生；联合使用与单独使用VU0364439及VU0364770对乳腺癌细胞增殖及凋亡的作用差异无统计学意义（P＞0.05）；RTFQ-PCR实验表明GRM4在MCF-7细胞中的表达水平最高；在MCF-7细胞中分别单独使用或联合使用VU0364439及VU0364770均能激活GRM4的表达。结论：GRM4的正向别构调节剂能够抑制乳腺癌细胞增殖并促进细胞凋亡，其作用可能是通过激活GRM4基因的表达引起的，本研究为探索GRM4在乳腺癌中的作用机制以及开发新的乳腺癌靶向治疗方法奠定了基础。

关键词: 代谢型谷氨酸受体4, 正向别构调节剂, 乳腺癌, 靶向治疗

Abstract: Background and purpose: Glutamate metabotropic receptor 4 (GRM4) is highly expressed in many tumors, and its expression is associated with the prognosis of patients. However, the function of GRM4 in breast cancer is still not clear. This study aimed to investigate the effects of positive allosteric modulators VU0364439 and VU0364770 on the proliferation and apoptosis of breast cancer cells, and then provide novel strategies for breast cancer targeted therapy. Methods: VU0364439 and VU0364770 were added solely or in combination into breast cancer cell lines MDA-MB-231, MCF-7 and SK-BR-3. The proliferation activities of these cells were detected using CellTiter- Glo^® luminescent cell viability assay. Annexin Ⅴ-PI double staining was used to detect the apoptosis of breast cancer cells. The expressions of GRM4 gene in six breast cancer cell lines were detected using real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR). After VU0364439 and VU0364770 were uesd solely or in combination, the expression of GRM4 gene was detected in the cell line with the highest GRM4 expression. Results: Compared with the control group, the proliferations of breast cancer cells MCF-7, MDA-MB-231 and SK-BR-3 were significantly inhibited after VU0364439 and VU0364770 were added solely or in combination. VU0364439 and VU0364770 also promoted the cell apoptosis of these breast cancer cell lines. The inhibitory effect of VU0364439 and VU0364770 on the proliferation of breast cancer cells was not significantly different when they were used in combination (P>0.05). RTFQ-PCR assay showed that the expression of GRM4 was higher in MCF-7 cells. The GRM4 expression could be activated when VU0364439 and VU0364770 were used solely or in combination. Conclusion: GRM4 positive allosteric modulators could inhibit breast cancer cell proliferation and promote cell apoptosis. This biological effect might function by activating GRM4 expression. This study lays the foundation for exploring the effect of GRM4 in breast cancer and developing novel strategies for breast cancer targeted therapy.

Key words: Glutamate metabotropic receptor 4, Positive allosteric modulators, Breast cancer, Targeted therapy

李林海,肖　斌,郭梓璇,等. GRM4正向别构调节剂抑制乳腺癌细胞的增殖并促进细胞凋亡[J]. 中国癌症杂志, 2018, 28(8): 561-566.

LI Linhai, XIAO Bin, GUO Zixuan, et al. GRM4 positive allosteric modulators inhibit breast cancer cell proliferation and promote cell apoptosis[J]. China Oncology, 2018, 28(8): 561-566.

[1]	章箎, 陈佳慧, 林瑾仪, 王妍, 张斯加, 朱玮, 程蕾蕾. 一种新型《乳腺癌治疗相关心血管毒性临床评分表》的价值分析[J]. 中国癌症杂志, 2022, 32(1): 54-60.
[2]	金奕滋, 林明曦, 张剑. DNA损伤应答缺陷作为乳腺癌治疗靶点的研究进展[J]. 中国癌症杂志, 2022, 32(1): 61-67.
[3]	《中国乳腺癌新辅助治疗专家共识（2022年版）》专家组. 中国乳腺癌新辅助治疗专家共识（2022年版）[J]. 中国癌症杂志, 2022, 32(1): 80-89.
[4]	张小艳, 李清祥, 刘　勇, 李　航, 仇丽娟, 封欣然, 谭立明 . HMGB1与乳腺癌患者临床病理学特征及免疫指标的相关性研究[J]. 中国癌症杂志, 2021, 31(9): 783-788.
[5]	曹爱玲, 曹　喆, 周　剑. 多西他赛联合胸腺肽α1对大鼠乳腺癌免疫微环境中Treg数量的影响及其机制研究[J]. 中国癌症杂志, 2021, 31(9): 799-806.
[6]	姚　嘉, 李冠乔, 杨时平, 苏慧銮 . Hsa-miR-98-5p/DKK3信号轴对乳腺癌细胞生物学行为的影响[J]. 中国癌症杂志, 2021, 31(9): 807-816.
[7]	丛斌斌, 王永胜. 激素受体阳性早期乳腺癌治疗现状与挑战[J]. 中国癌症杂志, 2021, 31(8): 689-696.
[8]	朱逸晖, 李　婷, 胡夕春. Trastuzumab deruxtecan的临床研究进展及展望——HER2耐药患者的新希望[J]. 中国癌症杂志, 2021, 31(8): 754-761.
[9]	丁高峰, 郭雷鸣, 陆寓非. 乳腺癌患者HER2和BRCA1表达与放疗敏感性的关系研究[J]. 中国癌症杂志, 2021, 31(7): 589-595.
[10]	金优萍, 李录英, 周　平. 长链非编码RNA STMN1P2在乳腺癌中的作用及机制研究[J]. 中国癌症杂志, 2021, 31(7): 596-604.
[11]	谢金芳, 曹春雨, 任　雪, 田家俊, 吕亚丰, 黄晓飞 . 萝卜硫素对小鼠乳腺癌4T1细胞上皮-间质转化、增殖和迁移的影响研究[J]. 中国癌症杂志, 2021, 31(7): 605-615.
[12]	朱　俊, 吴小华. 2020年度妇科恶性肿瘤最新研究进展及展望[J]. 中国癌症杂志, 2021, 31(4): 250-256.
[13]	曾　峰, 李　丹, 邵鑫鑫, 张能英, 陈星翰, 程晓明 . 基于SEER数据库构建1~2枚淋巴结阳性且乳房全切的老年早期乳腺癌患者不同腋窝手术方式的生存预测模型[J]. 中国癌症杂志, 2021, 31(4): 323-329.
[14]	王春建 , 聂　刚 , 毛　艳 . TRIP6在乳腺癌中的作用及其机制研究[J]. 中国癌症杂志, 2021, 31(3): 161-169.
[15]	胡喜娥, 杨振宇, 薛景毅, 杨　平, 彭书甲, 袁利娟, 包国强 . 单细胞测序在三阴性乳腺癌新辅助化疗中的应用研究进展[J]. 中国癌症杂志, 2021, 31(3): 221-226.

GRM4正向别构调节剂抑制乳腺癌细胞的增殖并促进细胞凋亡

GRM4 positive allosteric modulators inhibit breast cancer cell proliferation and promote cell apoptosis

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价