Effect And Mechanism Of Dechlorane Plus On MCF-7 Cell Migration

As a chlorinated flame retardant,Dechlorane Plus(DP)is widely distributed in different environmental matrices and biota.It can be easily accumuLated in the gonads.Our previous studies have shown that environmental related concentration of DP(10-6M)has an estrogen-like effect,via estrogen receptor a(ERa)-mediated genomic pathway and MAPK/ERK pathway.DP can induce the proliferation of MCF-7,an ER positive(ER+)human breast cancer cell line.There is no report about DP exposure on MCF-7 migration.Since the environment factor is considered to contribute about 70-95%in overall risk factors of breast cancer,and metastasis is responsible for more than 90%breast cancer death,the aim of this study is to investigate the environmental related concentration of DP exposure on MCF-7 migration and the possible molecuLar mechanisms.ResuLts obtained by Wound Healing and Transwell demonstrated DP of 10-6M couLd significantly increase the migration of MCF-7 cells.Two of G protein-coupled estrogen receptor 1(GPER)-mediated pathways,PI3K/AKT/mTOR and cAMP/PKA/CREB,were quantitative analyzed by Western blot.ResuLts proved that DP couLd activate PI3K/AKT/mTOR pathway by up-reguLation of PI3K,p-AKT,mTOR and p-mTOR,as well as cAMP/PKA/CREB pathway by up-reguLation of p-PKA and CREB.Moreover,both PI3K inhibitor(ly294002)and PKA inhibitor(H89)couLd significantly inhibit DP-induced MCF-7 cell migration.The resuLts obtained in this study further clarified the estrogen-like effects of DP,firstly identified the enhance effect of DP on human breast cancer cell migration and revealed the underlying mechanism is GPER-mediated PI3K/AKT/mTOR and cAMP/PKA/CREB pathways.Since the used exposure concentration of DP is environmental related,our resuLts will undoubtedly provide theoretical basis for toxicological and biological risk assessment of DP.