Endocrine Abstracts

Fenhexamid (Fen) is a fungicide used to treat the gray mold of fruits and vegetables. In this study, the ER positive-MCF-7 breast cancer cells were used to examine the effects of Fen on breast cancer progression. MCF-7 cells were cultured with 0.1% DMSO (control), 17β-estradiol (E2; 1×10⁻⁹ M) and Fen (10⁻⁵–10⁻⁷ M) in the absence or presence of ICI 182,780 (ICI, ER antagonist, 10⁻⁸ M) or Pictilisib (Pic, PI3K inhibitor, 10⁻⁷ M). In MTT assay, Fen increased MCF-7 viability about 2.5 times compared to a control like E2 (about 3 times). When co-treated with Pic or ICI, the cell viability increased by E2 or Fen was inhibited partially or completely. The cell viability increased by E2 or Fen was more inhibited by co-treatment with Pic and ICI than a single co-treatment of Pic or ICI. Likewise, E2 and Fen increased the ratio of MCF-7 cells that entered the S-phase of cell cycle, but co-treatment of Pic and ICI increased the cell ratio in the G0/G1-phase. And, the colony formation of MCF-7 cells was increased by E2 and Fen, while it was, in part, reversed in the presence of Pic or ICI and completely reversed by co-treatment with Pic and ICI. In wound-healing scratch assay, the scratched distance was reduced by MCF-7 cells treated with E2 or Fen compared with a control. However, the scratched distance was maintained to the control level by the co-treated with ICI or co-treatment with Pic and ICI. In migration assay, E2 or Fen increased migration of MCF-7 cells more than 5 times compared with a control, while co-treatment with ICI or co-treatment with Pic and ICI reversed E2 or Fen-induced migration. Collectively, Fen may induce cancer progression by increasing cell viability and migration via an ER dependent pathway and PI3K pathway. Hereafter, the mechanisms underlying the breast cancer progression induced by Fen will be identified by the examination on the protein expression of related genes.

Keywords: Fenhexamid, Estrogen receptor, PI3K/AKT pathway