The role of PI3K/AKT-related proteins in di(2-ethyl)hexylphthalate-induced BG-1 and MCF-7 cell proliferation, and inhibition by metformin

作者：Zhang, Jiatai; Zhao, Chenyang; Hu, Tengteng; Yang, Jipeng; Wu, Qian; Wang, Cheng^*; Dong, Shuying^*

来源：Immunopharmacology and Immunotoxicology, 2023, 45(3): 378-385.

DOI：10.1080/08923973.2022.2151915

• DEHP
• PI3K
• AKT
• ovarian cancer
• breast cancer
• metformin

ObjectiveTo investigate the molecular mechanism of the proliferation and migration of BG-1 and MCF-7cells induced by DEHP, and the antagonistic effect of metformin.MethodsThe proliferation, cell cycle progression, migration, and invasion abilities of BG-1 and MCF-7 cancer cells were examined via Cell Counting Kit-8, flow cytometry, Transwell, and scratch assays. E2F1, SKP2, cyclin D1, vimentin, E-cadherin, and GSK-3 beta, all of which play key roles in cancer development via the PI3K/AKT signaling pathway, were examined by immunofluorescence and immunocytochemistry.ResultsCell proliferation was significantly increased, and the wound closure and number of trans-membrane migrating cells were significantly increased, by DHEP treatment. The numbers of BG-1 and MCF-7 cells in the G0/G1 phase were significantly decreased, while those in the S phase were significantly increased. Increased E2F1, SKP2, cyclin D1, and vimentin levels and decreased E-cadherin and GSK-3 beta levels were detected in BG-1 and MCF-7 cells treated with DEHP compared to that in control cells. Furthermore, DEHP-induced effects were markedly inhibited by LY294002 (a PI3K/AKT inhibitor) or metformin.ConclusionWe demonstrated that DEHP-induced cell proliferation and migration involves the PI3K/AKT signaling pathway and that metformin can be used to inhibit this proliferation and migration.

• 单位
  哈尔滨医科大学