MEHP promotes breast cancer progression via GPR30-mediated epithelial-mesenchymal transition

  • Food Chem Toxicol. 2026 Jun:212:116049. doi: 10.1016/j.fct.2026.116049.
Wen Qi  1 ,  Jia Wang  1 ,  Yunlong Wang  2 ,  Jianwei Cui  1 ,  Xiaotong Wu  1 ,  Ziji Ding  1 ,  Tao Jiang  1 ,  Wanyu Liu  1 ,  Xueyu Zhai  1 ,  Shunzi Jin  3 ,  Lin Ye  4
Affiliations
  • 1. Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, China.
  • 2. Department of Radiotherapy, Tumor Hospital of Jilin Province, Changchun, China.
  • 3. NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, China. Electronic address: [email protected].
  • 4. Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, China. Electronic address: [email protected].
PMID: 41780712 DOI: 10.1016/j.fct.2026.116049
Abstract

Purpose: Mono-(2-ethylhexyl) phthalate (MEHP), the primary metabolite of di-(2-ethylhexyl) phthalate (DEHP), is a well-documented environmental endocrine disruptor with estrogen-like effects that promote the development of hormone receptor-positive tumors. G protein-coupled receptor 30 (GPR30), also known as G protein-coupled Estrogen receptor 1, has emerged as a key factor in the pathogenesis and progression of hormone-dependent tumors. This study elucidates the mechanism by which MEHP promotes breast Cancer development via GPR30.

Methods: MCF-7 cells were exposed to different concentrations of MEHP, and GPR30 expression was inhibited using G15. Cell proliferation and cell cycle were assessed using the CCK-8 and flow cytometry, respectively. Cell migration and cell invasion were evaluated via scratch-wound assays and transwell migration assay. Western blotting and quantitative real-time Reverse transcription PCR were performed to analyze the expression of GPR30 and epithelial-mesenchymal transition (EMT)-related mRNAs and proteins.

Results: Our findings demonstrate that MEHP exposure promotes the proliferation, migration, and invasion of MCF-7 cells, while concomitantly modulating the expression of GPR30, cell cycle-related and EMT-associated mRNAs and proteins. After inhibiting GPR30, the promoting effect of MEHP on MCF-7 cell proliferation and migration decreased.

Conclusion: Notably, GPR30 inhibition attenuated MEHP-induced promotion of MCF-7 cell proliferation and migration through modulating the EMT process.

Keywords
Breast cancer; EMT; GPR30; MEHP; Migration; Proliferation.
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