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

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Abstract

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.

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Acknowledgments

We thank Dr. Guowei Gu (Calabria, Italy) for the gift of Plasmid pCMV5-hERβ. We are also grateful to Professor Tao Xi (Nanjing, China) for the supports during this study. This research was supported by the Natural Science Foundation Committee of China (NSFC 30672015, 30700779, 30800257, 30970776, 81000666, 81071194, 31050110123, 81171395) and the major project from the Ministry of Science and Technology for new drug development (2009ZX09310-004).

Conflict of interest

The authors have no conflicts to disclose.

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Authors and Affiliations

  1. Department of Biomedical Engineering, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China

    Zhenzhen Tu, Yuxiang Ma, Junmei Tian, Hui Li & Yueqing Gu

  2. Department of Radiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA

    Walter Akers & Samuel Achilefu

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  1. Zhenzhen Tu
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Correspondence to Yueqing Gu.

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Tu, Z., Ma, Y., Tian, J. et al. Estrogen receptor β potentiates the antiproliferative effect of raloxifene and affects the cell migration and invasion in HCT-116 colon cancer cells. J Cancer Res Clin Oncol 138, 1091–1103 (2012). https://doi.org/10.1007/s00432-011-1145-3

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