MPEP阻断mGlu5抑制肝癌细胞HepG2增殖  

Blockade of mGlu5 with MPEP could Inhibit HepG2 Cell Proliferation

作　　者：袁记方[1,2] 张晨光[3] 王舒婷[1,2] 赵树东[4] 张红[1,2] 

机构地区：[1]首都医科大学神经生物学系,教育部神经退行性疾病重点实验室,北京100069 [2]首都医科大学细胞生物学系,北京100069 [3]首都医科大学医学遗传学系,北京100069 [4]首都医科大学基础医学院,北京100069

出　　处：《中国生物化学与分子生物学报》2013年第4期338-346,共9页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No.81201816;81171886;30973406);北京市自然科学基金资助项目(No.5102011)~~

摘　　要：代谢型谷氨酸受体5(metabotropic glutamate receptors 5,mGlu 5)在神经系统的多种病理生理过程中发挥重要作用.mGlu5与肝细胞癌的发生发展关系密切,其抑制剂2-甲基-6-(苯乙基)-吡啶(2-methyl-6-(phenylethyl)-pyridine,MPEP)能够促进肝癌细胞凋亡,抑制肝癌细胞的迁移.在此基础上,进一步探讨了MPEP与肝癌细胞增殖之间的关系.结果显示:在无血清和有血清的条件下,MPEP均能显著降低肝癌细胞HepG2的细胞活力.同时发现,有血清条件下MPEP能使HepG2细胞周期停滞在G1期,显著降低HepG2细胞的DNA合成能力和克隆形成能力,并能下调细胞增殖信号ERK通路的活性.该研究结果为进一步认识MPEP对肝癌细胞的抑制作用提供了新的实验证据.Metabotropic glutamate receptor 5 （mGlu5） is known to be involved in multiple pathophysiologic processes of the nervous system, mGlu5 was also closely related to the initiation and progression of hepatocellular carcinoma （ HCC ）. 2-Methyl-6-（phenylethyl） - pyridine （ MPEP）, as the specific antagonist of mGluS, could promote the apoptosis and inhibit the migration of hepatocellular carcinoma （HCC） cells. The effect of MPEP on HCC cell proliferation was further explored. The results showed that treatment of HepG2 cells with MPEP dramatically down-regulated the viability of the cells in both presence and absence of fetal bovine serum. Moreover, it was found that MPEP treatment significantly attenuated colony formation of HepG2 cells, decreased the DNA synthesis as evidenced with 5-ethynyl-2＇-deoxyuridine （EdU） incorporation assays. Furthermore, cell cycle analysis with flow cytometry indicated that MPEP treatment induced G1 arrest in HepG2 cells. Meanwhile, the activity of extracellular regulated protein kinases （ERK） was down- regulated by MPEP. We also found that MPEP increased the reactive oxygen species （ROS） level of HepG2 cells; however, inhibition of ROS did not affect the inhibitory effect of MPEP. These results will provide new evidence for understanding the inhibitory effect of MPEP on HCC.

关 键 词：代谢型谷氨酸受体5 2-甲基-6-(苯乙基)-吡啶 肝细胞癌 细胞增殖 

分 类 号：Q2[生物学—细胞生物学]