2019: Articles in Press
Research Article

Wogonin Disrupts the ER-α36/EGFR Signaling Loop and Sensitizes Triple-negative Breast Cancer Cells to Tamoxifen

Junhun Shao
Beijing Shenogen Biomedical Co., Ltd, #29 Life Science Park Road, Beijing, P.R.China
Ze Li
Beijing Shenogen Biomedical Co., Ltd, #29 Life Science Park Road, Beijing, P.R. China
Sisi Bei
Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, Guangxi 541001, P.R. China
Libin Song
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, 270 Dong’an Road, Shanghai, 200032, P.R.China
Qi Qi
Department of Integrative Oncology, Fudan University Shanghai Cancer Center,270 Dong’an Road, Shanghai, 200032, P.R. China
Zhaoyi Wang
Beijing Shenogen Biomedical Co., Ltd, #29 Life Science Park Road, Beijing, P.R. China
Guangying Qi
Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, Guangxi 541001, P.R. China
Published October 16, 2019
Keywords
  • ER-α36,
  • Wogonin,
  • Triple-negative breast cancer,
  • Growth inhibition,
  • The ER-36/EGFR signaling loop

Abstract

Introduction: Triple-negative breast cancer (TNBC) is a sub-class of breast cancer that is deficiency of progesterone receptor (PR),estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2), which is often highly malignant and lacks effective treatment. Recent studies revealed that an isoform of estrogen receptor-alpha, ER-α36, is expressed in TNBC and plays an important role in TNBC growth. ER-α36 forms a positive regulatory loop with epidermal growth factor receptor (EGFR) and positively regulates each other’s expression. Thus, the ER-α36/EGFR signaling loop is a potential target for development of novel therapeutic agents for TNBC. In this report, we assessed the effects of wogonin, a naturally flavone derivative purified from the root of Scutellaria baicalensis Georgi, on growth of TNBC cells and examined the potential mechanism of action.
Methods: Cell growth assay was used to assess the effects of wogonin on growth of TNBC cells stimulated by estrogen and EGF. Western blot analysis was used to examine the molecular action of wogonin.
Results: Our study indicated that wogonin down-regulated both ER-α36 and EGFR expression, and inhibited growth of TNBC MDA-MB-436 and MDA-MB-231cells. We also found that wogonin conferred TNBC cells sensitivity to anti-estrogen tamoxifen.
Conclusions: Our results suggested that wogonin has a potential to be developed into a novel therapeutic agent for TNBC and suggested that targeting the ER-α36/EGFR signaling loop is a new approach to overcome the tamoxifen insensitivity of TNBC.