2. Academic Validation
  3. BPA exposure enhances the metastatic aggression of ovarian cancer through the ERα/AKT/mTOR/HIF-1α signaling axis

BPA exposure enhances the metastatic aggression of ovarian cancer through the ERα/AKT/mTOR/HIF-1α signaling axis

  • Food Chem Toxicol. 2023 Apr 18;113792. doi: 10.1016/j.fct.2023.113792.
Xin Xie 1,  Yan Zhu 1,  Huimin Cheng 1,  Haili Li 1,  Yadi Zhang 1,  Rong Wang 1,  Wenyong Li 2,  Fengrui Wu 3
Affiliations

Affiliations

  • 1 Province Key Laboratory of Environmental Hormone and Reproduction, Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation, Fuyang Normal University, 100 Qinghe West Road, Fuyang, Anhui, 236041, PR China.
  • 2 Province Key Laboratory of Environmental Hormone and Reproduction, Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation, Fuyang Normal University, 100 Qinghe West Road, Fuyang, Anhui, 236041, PR China. Electronic address: liwenyong@aliyun.com.
  • 3 Province Key Laboratory of Environmental Hormone and Reproduction, Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation, Fuyang Normal University, 100 Qinghe West Road, Fuyang, Anhui, 236041, PR China. Electronic address: fengruiwu@fynu.edu.cn.
PMID: 37080528 DOI: 10.1016/j.fct.2023.113792
Abstract

Long-term exposure to bisphenol A (BPA) in humans may promote ovarian Cancer development. In present study, the mechanisms by which BPA mediates the aggression metastatic behavior of ovarian Cancer were investigated in vitro/in vivo. The results showed that BPA (10 μM) significantly promoted the proliferation, migration and invasion of human ovarian Cancer cells (ES-2 and OVCAR-3 cells); moreover, it promoted ES-2 and OVCAR-3 cell glucose uptake, lactic acid release and intracellular ATP synthesis. After administration of 5 μg/kg/day BPA, tumor volume was increased compared with that in control group. KEGG and GO enrichment analyses showed that the genes from ES-2 cell in 10 μM BPA-treated group were enriched mainly in central carbon metabolism and PI3K-AKT signaling pathway. Then, qRT‒PCR and western blotting results showed that BPA (10 μM) increased the mRNA and protein expression levels of glycolysis-related genes and mTOR, p-AKT HIF-1α and ERα in vitro/vivo; whereas this effect was reduced after treatment with the ERα Inhibitor methyl-piperidino-pyrazole. Furthermore, coimmunoprecipitation and mass spectrometry showed that BPA promoted the direct interaction of ERα with Lactate Dehydrogenase A. These results show that BPA directly promoted the proliferation, migration and invasion of ovarian Cancer cells through the ERα/Akt/mTOR/HIF-1α signaling axis to enhance glycolysis.

Keywords

Bisphenol A; ERα/AKT/mTOR/HIF-1α signaling axis; Glycolysis; Metastatic aggression; Ovarian cancer.

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