Fig. 6
From: Inhibition of TPL2 by interferon-α suppresses bladder cancer through activation of PDE4D
Synergistic antitumor effect of IFN-α and roflumilast on MIBC. (a) In MIBC, TPL2 is phosphorylated and activates IKK complexes. Therefore, NF-κB is activated and results in COX-2 overexpression that promotes the MIBC development. Moreover, TPL2 induces COX-2 expression by the enhancement of cAMP/CREB signaling through ERK-mediated inhibition of PDE4D activity. (b) IFN-α-induced TPL2 inhibition leads to down-regulation of COX-2 expression and exerts the anti-tumor effect in MIBC treatment. PDE4D induction by roflumilast synergizes with IFN-α activity to inhibit COX-2 expression through the reduction of cAMP level and potentiates the anti-tumor effect of IFN-α on MIBC