Department of Chemistry, Tamkang University, New Taipei, Taiwan, R.O.C.
Department of Early Childhood Care and Education, University of Kang Ning, Taipei, Taiwan, R.O.C.
Environ Toxicol. 2023 Jul;38(7):1609-1617. doi: 10.1002/tox.23790. Epub 2023 Mar 29.
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.
HER2 癌基因的上调与多种人类癌症相关，并与预后不良相关。黄芩素被报道具有抗肿瘤活性，但这种效应在 HER2 阳性癌细胞中的分子机制尚未得到研究。在这项研究中，我们的数据表明，黄芩素可以抑制过表达 HER2 的卵巢癌细胞的增殖和转化潜能。黄芩素处理导致 HER2 基因表达在转录水平上呈剂量依赖性抑制。黄芩素作用于过表达 HER2 的卵巢癌细胞，下调 HER2 下游的 PI3K/Akt 信号通路，并抑制下游靶标，如 VEGF、cyclin D1 和 MMP2 的表达或活性。用药物赋形剂补充黄芩素的口服给药显著抑制了小鼠中过表达 HER2 的卵巢 SKOV-3 癌异种移植物的生长。这些结果表明，黄芩素在转录水平下调 HER2 基因表达有助于抑制过表达 HER2 的卵巢癌细胞的体外和体内增殖以及 HER2 介导的恶性转化。
