Study on Multidrug Resistance of Triple Negative Breast Cancer Cells MDA-MB-23 Mediated by PI3K/Akt/NF-κB Pathway Through P-gp

Multidrug resistance (MDR) is the dominating obstacle to the chemotherapy. Many studies show that the PI3K signaling pathway is involved in MDR phenotype, however, the mechanism of MDR is still unknown. This study tended to investigate the regulating effect of PI3K/Akt signaling pathway and its downstream target genes in P-gp-mediated MDR in MDA-MB-231/ADR cells. MDA-MB-231/ADR cells were pretreated by PI3K selective inhibitor LY294002 (20 mu mol/L) for 2 h, the sensitivity of ADR was evaluated by the cell counting kit-8 assay, and the expressions of P-gp, LRP, MRP-2, Akt, p-Akt, I kappa B and p-I kappa B were evaluated by Western blot. The activity of ABCB1 promoter was evaluated by CHIP. After inhibiting the activity of PI3K/Akt signaling pathway, the IC50 of ADR decreased from 16.40 +/- 2.41 mu mol/L to 3.60 +/- 0.10 mu mol/L in MDA-MB-231/ADR cells, and RI was 7.20. The expressions of P-gp, p-Akt and p-I kappa B were down-regulated in comparison with that of the control group (P < 0.05), but the expressions of LRP, MRP-2, Akt and I kappa B did not change significantly (P > 0.05). CHIP result has confirmed that NF-kappa B protein could bind to the region of ABCB1 gene promoter in MDA-MB-231/ADR cells. Blocking of PI3K/Akt/NF-kappa B signal pathway could increase the drug sensitivity of MDA-MB-231/ADR cells, inhibit the phosphorylation of p-Akt and p-I kappa B, and reverse MDR of breast cancer cells.