Fig. 4.

Association of CXCR2 with MAPK, STAT3, PI3K/AKT, and NF-κB signaling pathways. Silencing of CXCR2 expression reduced activation of MAPK p38, MEK1/2, ERK1/2, JNK1/2, and STAT3 (A, top) as well as the expression of the angiogenic factor VEGF, but enhanced the expression of antiangiogenic TSP-1 (A, bottom panels), which was confirmed by decreased tissue microvessel density (arrows) after staining with CD34 in xenograft tumor tissues derived from nude mice injected with SKOV3/CXCR2i cells compared with tissues derived from mice given SKOV3/GFPi cells (B). Error bars, 95% confidence intervals. Silencing of CXCR2 expression also altered the expression of PI3K/AKT in a cell line–dependent manner (C, top panels). Although the upstream molecules in the NF-κB signaling pathway, including NIK, IKKα, and IKKβ, were inconsistently changed in different cell lines with CXCR2 shRNA, the expression of IκBα and the nuclear and cytosolic accumulation of NF-κB subunit p65 were constantly either decreased or increased (C, bottom panels). The binding activity of NF-κB nuclear extract with its DNA consensus oligos declined remarkably after CXCR2 was stably silenced (D).