RESUMO
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.
Assuntos
Antineoplásicos/farmacologia , Fator de Iniciação 4E em Eucariotos/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Carcinoma Anaplásico da Tireoide/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Modelos Animais de Doenças , Humanos , Camundongos , Fosforilação , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Sirtuin 1, a nicotinamide adenine dinucleotide-dependent deacetylase that is highly expressed in the hippocampus and anterior cortex tissues related to Alzheimer's Disease pathology, can cross the blood-brain barrier and is a promising biomarker. METHODS: A 1:1:1 case-control study was conducted and serum fasting blood glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, SIRT1, IL-6, Aß1-42, T-tau and P-tau-181 levels were evaluated in blood samples of 26 patients form the Alzheimer's Disease group, 26 patients form the mild cognitive impairment group, and 26 individuals form the normal control group. Receiver operator characteristic curves were used to evaluate the diagnostic significance. RESULTS: Serum SIRT1 level was significantly down-regulated in the mild cognitive impairment patients and Alzheimer's Disease patients compared with that in the normal control group (P<0.05). ROC curve analysis demonstrated that SIRT1 was a promising biomarker to distinguish Alzheimer's Disease patients from the mild cognitive impairment patients and the normal control group. In addition, SIRT1 was estimated to perform well in the diagnosis of Alzheimer's Disease ([AUC] = 0.742). CONCLUSIONS: In summary, the present study suggested that serum SIRT1 might be an early promising diagnostic biomarker for Alzheimer's Disease.