Kun Hu1, Juan Zhang2, Min Yu3, Chang'e Xiong4. 1. Thyroid Surgery Department, The Second Clinical Medical College, Yangtze University, Jingzhou Central Hospital, Jingzhou, People's Republic of China. 2. Endocrinology Department, The Second Clinical Medical College, Yangtze University, Jingzhou Central Hospital, Jingzhou, People's Republic of China. 3. Galactophore Department, The Second Clinical Medical College, Yangtze University, Jingzhou Central Hospital, Jingzhou, People's Republic of China. 4. School of Basic Medical Sciences, Hubei University of Science & Technology, Xianning, People's Republic of China.
Abstract
AIM: We investigated whether MAPK-interacting kinase (Mnk) inhibition sensitizes anaplastic thyroid cancer (ATC) cellular response to chemotherapy. MATERIALS & METHODS: In vitro and in vivo methods were used to examine the combinatory effects of cisplatin with Mnk inhibition and its underlying mechanism. RESULTS: 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. CONCLUSION: Targeting Mnk-eIF4E pathway provides a therapeutic strategy by sensitizing ATC response to chemotherapeutic drug.
AIM: We investigated whether MAPK-interacting kinase (Mnk) inhibition sensitizes anaplastic thyroid cancer (ATC) cellular response to chemotherapy. MATERIALS & METHODS: In vitro and in vivo methods were used to examine the combinatory effects of cisplatin with Mnk inhibition and its underlying mechanism. RESULTS: 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. CONCLUSION: Targeting Mnk-eIF4E pathway provides a therapeutic strategy by sensitizing ATC response to chemotherapeutic drug.
Entities:
Keywords:
Mnk; chemotherapy; eIF4E; thyroid cancer