Activation of GPER suppresses the malignancy of osteosarcoma cells via down regulation of IL-6 and IL-8

作者：Zha, Zhuqing; Su, Anping; Huo, Shaochuan^*

来源：Archives of Biochemistry and Biophysics, 2018, 660: 149-155.

DOI：10.1016/j.abb.2018.10.018

• GPER
• Migration
• IL-6
• IL-8
• Osteosarcoma
• p65

Estrogenic signals can regulate the progression of osteosarcoma (OS) via classic estrogen receptor alpha/beta (ER alpha/beta). G protein-coupled estrogen receptor (GPER) can mediate the non-genomic effects of estrogen and regulate the progression of various cancers. Our present study revealed that the expression of GPER in OS cells and tissues was lower than that in their corresponding controls. Activation of GPER via its specific agonist G-1 can decrease the proliferation, migration, and invasion of OS cells. By screening the expression of cytokines involved in the progression of OS, we found that activation of GPER can inhibit the expression of interleukin-6 (IL-6) and IL-8 in OS cells. Recombinant IL-6 (rIL-6) or rIL-8 can attenuate G-1 suppressed migration of OS cells. Mechanically, activation of GPER can rapidly decease the phosphorylation and nuclear translocation of NF-kappa B in OS cells. While over expression of p65 significantly attenuated G-1 induced down regulation of IL-6/IL-8. Further, G-1 can decrease the activation of p38-MAPK, which can further shorten the half-life of IL-8 mRNA. Collectively, we revealed that GPER can suppress the migration and invasion of OS cells via inhibition of IL-6 and IL-8. It suggested that GPER might be a potential therapy target for OS treatment.

• 出版日期2018-12-15
• 单位南方医科大学; 广州中医药大学; 河南省正骨研究院