Wogonin Disrupts the ER-α36/EGFR Signaling Loop and Sensitizes Triple-negative Breast Cancer Cells to Tamoxifen
- Triple-negative breast cancer,
- Growth inhibition,
- The ER-36/EGFR signaling loop
Copyright (c) 2019 Shao et al.
This work is licensed under a Creative Commons Attribution 4.0 International License.
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.