Estrogen receptor β potentiates the antiproliferative effect of raloxifene and affects the cell migration and invasion in HCT-116 colon cancer cells

Background: Estrogen receptor β (ERβ) is the predominant ER in the colorectal epithelium, whose expression is greatly reduced in colorectal cancer compared with normal colon tissue. Recent in vitro studies suggested that ERβ may suppress tumor growth. No research was reported whether ERβ can be used as therapeutic agent for colon cancer. Methods: In this study, ERβ gene constructed into adenoviral (Ad) vectors was used to treat colon cancer HCT-116 cells alone or in combination with raloxifene. In vitro and in vivo studies were conducted to investigate the therapeutic effects of ERβ and raloxifene in HCT-116 cells. Results: Our results indicated that, although Ad-ERβ alone had no effect on the proliferation of HCT-116 cells, the combination of Ad-ERβ with raloxifene significantly inhibited the proliferation of HCT-116 cells. The apparently apoptotic induction effects may partly explain the cytotoxicity of the two agents. The results of the study of ERβ on migration and invasion of HCT-116 cells demonstrated that overexpression of ERβ significantly decreased cell migration and increased invasion of cells. The antitumor efficacies of ERβ as well as raloxifene were further investigated on HCT-116 tumor bearing mice. Results demonstrated that both Ad-ERβ and raloxifene individually inhibited tumor growth. The combination group showed the highest inhibitory efficiency compared with other three groups. Conclusion: These findings demonstrated that combined administration of Ad-ERβ with raloxifene represents a promising colon cancer therapeutic strategy.