Fig. 5: Ivermectin interacted with FOXA1 to block pioneer factor activity.
From: Integrated analysis reveals FOXA1 and Ku70/Ku80 as targets of ivermectin in prostate cancer
A GSEA showed that genes induced by FOXA1 were inhibited by ivermectin in C4-2 cells. B RT-qPCR analysis of FOXA1 induced genes (CDKN3, CDCA2, and CAMKK2) and FOXA1 repressed EMT-associated genes (MET, MMP7, and SOX9) in C4-2 cells treated with ivermectin for 48 h. C Western blot analysis of FOXA1 and N-cadherin in LNCaP and C4-2 cells treated with ivermectin for 48 h. D ChIP–qPCR analysis for FOXA1 or AR occupancy, and FAIRE–qPCR analysis of chromatin accessibility at a target regulated by AR and FOXA1 (KLK3 and NKX3-1) in C4-2 cells treated with ivermectin. E ChIP–qPCR analysis for FOXA1 and FAIRE-PCR analysis of chromatin accessibility at a target regulated by FOXA1 (E2F1 and MET) in C4-2 cells treated with ivermectin. F FOXA1 knockdown impaired the ivermectin-repressed expression of KLK3 and E2F1 genes. mRNA levels were measured 48 h after the implementation of the ivermectin treatment and siRNA transfection by RT-qPCR in C4-2 cells. G, H Western blots showing thermostable FOXA1 and AR following indicated heat shocks in the presence (+) or absence (−) of 50 μM ivermectin in LNCaP (G) and C4-2 (H) cells. I Western blots showing thermostable FOXA1 following indicated heat shocks in the presence (+) or absence (−) of 50 μM ivermectin in 22RV1 cells. J GSEA showed the inactivation of FOXA1 induced genes in 22RV1 cells after the ivermectin treatment. K RT-qPCR analysis of FL-AR and ARv7 in 22RV1 cells treated with ivermectin for 48 h. L ChIP–qPCR analysis for FOXA1 and FAIRE–qPCR analysis of chromatin accessibility at KLK3 and E2F1 in 22RV1 cells treated with ivermectin.
