OncoTargets and Therapy (Nov 2019)
Estrogen Receptor Beta Inhibits The Proliferation, Migration, And Angiogenesis Of Gastric Cancer Cells Through Inhibiting Nuclear Factor-Kappa B Signaling
Abstract
Yiping Zhang, Yahua Wu, Xufeng Zhou, Benyi Yi, Lili Wang Department of Biochemistry and Molecular Biology, Basic Medical College of Jiujiang University, Jiujiang City, Jiangxi Province 332000, People’s Republic of ChinaCorrespondence: Yiping ZhangDepartment of Biochemistry and Molecular Biology, Basic Medical College of Jiujiang University, No. 320, Xunyang East Road, Xunyang District, Jiujiang City, Jiangxi Province 332000, People’s Republic of ChinaTel +86-13767275087Email [email protected]: This study aimed to investigate the regulatory roles of estrogen receptor beta (ERβ) on gastric cancer (GC) cells, and reveal the potential mechanisms relating to nuclear factor-kappa B (NF-κB) signaling.Methods: GC cell lines SGC7901 and MKN45 were transfected with pEGFP-C1-ERβ to overexpress ERβ, and treated with PMA (a NF-κB activator) to activate NF-κB signaling. The cell proliferation and migration, as well as the formation of vessel-like structures in human venous endothelial cells (HUVECs) were detected. The expression of ERβ, NF-κB p65, p-NF-κB p65, Ki67 (a proliferation marker), vascular endothelial growth factor A (VEGF-A) and matrix metalloproteinase 2 (MMP-2), the DNA binding activity of NF-κB p65, the content of VEGF-A, and the activity of MMP-2 were detected in SGC7901 and MKN45 cells.Results: The transfection of pEGFP-C1-ERβ significantly increased the expression of ERβ in SGC7901 and MKN45 cells (P < 0.05). Overexpression of ERβ in SGC7901 and MKN45 cells significantly decreased the cell activity, cell number in G2/M phase, cell migration, the expression of Ki67, VEGF-A and MMP-2, VEGF-A content, MMP-2 activity, as well as the number of vessel-like structures formed by HUVECs (P < 0.05). Overexpression of ERβ also significantly decreased the DNA binding activity and the expression of p-NF-κB p65 in SGC7901 and MKN45 cells (P < 0.05). The anti-tumor effect of ERβ overexpression on GC cells was reversed by the intervention of PMA (P < 0.05).Conclusion: Overexpression of ERβ inhibited the proliferation, migration, and angiogenesis of GC cells through inhibiting NF-κB signaling.Keywords: estrogen receptor beta, gastric cancer, nuclear factor-kappa B, angiogenesis, proliferation
