Purpose: This study aimed to explore the role of Estrogen Receptor-β (ERβ)-mediated Notch signaling pathway in the regulation of proliferation and apoptosis in liver cancer cells.
Methods: HepG2 cells (Pbi-EGFP-ER) were transfected with ERβ that mediated by liposome, and normal HepG2 cells (Blank) and empty plasmid-transfected HepG2 cells (Pbi-EGFP-C) were used as controls. Then, Huh7 cells were transfected with shERβ lentivirus to knock down ERβ expression. The Huh7 cells were divided into three groups including Blank, experimental group (shERβ) and negative group (shLuc). Then, qRT-PCR, Western blot, CCK-8 assay, cell scratch assay, Transwell assay, Annexin V-FITC and PI double staining were performed based on these groups. Finally, a mouse xenograft model was constructed to verify the regulation of ERβ on Notch signaling pathway in liver cancer.
Results: In HepG2 cells, the ERβ expression in Pbi-EGFP-E group was higher than that in Blank and Bi-EGFP-C group. Overexpression of ERβ inhibited HepG2 cell proliferation, migration, invasion and Ki67 protein expression, as well as promoted apoptosis, Bcl-2 and Bax expression. Overexpression of ERβ decreased Notch1, Notch2 and Hes1 expression. In Huh7 cells, the effect of low ERβ expression was contrary to that of high ERβ expression. The shERβ + DAPT group reversed the effect of shERβ on the volume and weight of transplanted tumors.
Conclusion: ERβ may inhibit the development of liver cancer and promote apoptosis via inhibiting the Notch pathway.
Keywords: liver cancer, ERβ, Notch signaling pathway, HepG2 and Huh7, proliferation and apoptosis