Long-Term Alteration of Reactive Oxygen Species Led to Multidrug Resistance in MCF-7 Cells

Figure 10

PI3K/Akt, Nrf2, and HIF-1α signaling pathways involved in ROS-induced MDR in MCF-7 cells. (a) PI3K/Akt, Nrf2, and HIF-1α inhibition increased the inhibition rate of MCF-7/ROS cells (MCF-7 cells were treated with 0.1 μM H₂O₂ for 20 weeks) by ADM. MCF-7/ROS cells were treated with 125 μM ADM, 125 μM ADM + 10 μM LY294002, 125 μM ADM + 5 μM YC-1, or 125 μM ADM + Si-Nrf2 for 48 h, and then the inhibition rate was determined by MTT assay. Data represents the mean ± SD, , and significant differences relative to MCF-7/ROS cells which only received 125 μM ADM were indicated as . (b) Protein levels of PTEN, PI3K, Akt, p-Akt, Nrf2, HIF-1α, P-gp, and GSTπ in MCF-7 cells (group 1) and MCF-7/ADM cells (group 2) and in MCF-7/ROS cells which received 10 μM LY294002 (group 4), Si-Nrf2 (group 5), or 5 μM YC-1 (group 6) treatment for 48 h were determined by western blot. Data represents the mean ± SD, , and significant differences relative to control group (MCF-7/ROS cells, group 3) were indicated as and .

(a)

(b)