PTGS2 and osteosarcoma: In summary, ZD6474 exerts direct antitumor effects on osteosarcoma cells in vitro and in xenograft nude mouse model through inhibiting the activation of EGFR pathway and consequently suppressing downstream PI3k/Akt and MAPK/ERK pathways, and the combination of ZD6474 with celecoxib demonstrated a synergistic/additive antitumor effect by the interaction and regulation of EGFR and COX-2/PGE2 pathway (a schematic diagram was shown in Figure 7).