Baicalein suppresses HER2‐mediated malignant transformation of HER2‐overexpressing ovarian cancer cells by downregulating HER2 gene expression

The upregulation of the HER2 oncogene is associated with a variety of human cancers and is associated with poor prognosis. Baicalein is reported to have anti‐tumor activity, but the molecular mechanism of this effect in HER2‐positive cancer cells has not been studied. In this study, our data showed...

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Veröffentlicht in:Environmental toxicology 2023-07, Vol.38 (7), p.1609-1617
Hauptverfasser: Chuang, Tzu‐Chao, Fang, Guan‐Shiun, Hsu, Shih‐Chung, Lee, Yi‐Jen, Shao, Wei‐Syun, Wang, Vinchi, Lee, Shou‐Lun, Kao, Ming‐Ching, Ou, Chien‐Chih
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Sprache:eng
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Zusammenfassung:The upregulation of the HER2 oncogene is associated with a variety of human cancers and is associated with poor prognosis. Baicalein is reported to have anti‐tumor activity, but the molecular mechanism of this effect in HER2‐positive cancer cells has not been studied. In this study, our data showed that baicalein can inhibit the proliferation and transformation potential of ovarian cancer cells overexpressing HER2. Baicalein treatment caused a dose‐dependent inhibition of HER2 gene expression at the transcriptional level. Baicalein acted on ovarian cancer cells overexpressing HER2 to downregulate the PI3K/Akt signaling pathway downstream of HER2 and inhibit the expression or activity of downstream targets, such as VEGF and cyclin D1 and MMP2. Oral administration of baicalein supplemented with a pharmaceutical excipient significantly inhibited the growth of HER2‐overexpressing ovarian SKOV‐3 cancer xenografts in mice. These results suggest that downregulation of HER2 gene expression by baicalein at the transcriptional level contributes to inhibit the in vitro and in vivo proliferation and HER2‐mediated malignant transformation of HER2‐overexpressing ovarian cancer cells.
ISSN:1520-4081
1522-7278
DOI:10.1002/tox.23790