Propoxur enhances MMP-2 expression and the corresponding invasion of human breast cancer cells via the ERK/Nrf2 signaling pathway

Propoxur is considered a prime etiological suspect of increasing tumor incidence, but the role is still undefined. In this study, two human breast cancer cells lines, MCF-7 and MDA-MB-231 cells, were used as cell models. Cells were respectively treated with 0, 0.01, 1, or 100 μM propoxur. PD98059, a MEK inhibitor, was administered to block the ERK/MAPK pathway. Migration and reactive oxygen species were measured by wound healing and Transwell assays, and flow cytometry. Protein expression and subcellular location were detected by western blotting and immunofluorescence staining, respectively. Results showed that propoxur treatment enhanced cell migration and invasion in a dose-dependent manner, while MMP-2 expression, but not MMP-9, was significantly increased in two cell lines. Meanwhile, the treatment increased intracellular reactive oxygen species, Nrf2 expression and nuclear translocation, and ERK1/2 phosphorylation. Inversely, inhibition of ERK1/2 activation with PD98059 significantly attenuated propoxur-induced Nrf2 expression and nuclear translocation. Moreover, PD98059 suppressed propoxur-induced cell migration and invasion, and MMP-2 overexpression. Collectively, these results indicate that propoxur can trigger reactive oxygen species overproduction, further promoting breast cancer cell migration and invasion by regulating the ERK/Nrf2 signaling pathways.