MPEP阻断mGlu5抑制肝癌细胞HepG2增殖

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.

Blockade of mGlu5 with MPEP could Inhibit HepG2 Cell Proliferation

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 mGlu5,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.