Inhibition of Mnk-eIF4E pathway sensitizes the efficacy to chemotherapy in anaplastic thyroid cancer.

Abstract

We investigated whether MAPK-interacting kinase (Mnk) inhibition sensitizes anaplastic thyroid cancer (ATC) cellular response to chemotherapy. In vitro and in vivo methods were used to examine the combinatory effects of cisplatin with Mnk inhibition and its underlying mechanism. Mnk inhibition by pharmacological or genetic approaches inhibits proliferation and induces apoptosis of ATC cells and enhances the effects of cisplatin in in vitro and in vivo. Mechanistically, cisplatin increases eIF4E phosphorylation in a dose- and time-dependent manner in ATC cells. Mnk inhibitors sensitize the efficacy of cisplatin by inhibiting cisplatin-induced eIF4E phosphorylation. Targeting Mnk-eIF4E pathway provides a therapeutic strategy by sensitizing ATC response to chemotherapeutic drug.