二甲双胍抑制分化型甲状腺癌的作用及机制

Effects and mechanisms of metformin on differentiated thyroid cancer

二甲双胍是治疗糖尿病的一线药物,晚近其抗肿瘤效应受到广泛关注。研究发现,服用二甲双胍的2型糖尿病患者分化型甲状腺癌(differentiated thyroid cancer,DTC)的风险降低,其机制可能与一方面通过改善胰岛素抵抗、下调促甲状腺激素(thyroid-stimulating hormone,TSH)和激活腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)通路抑制DTC细胞增殖,一方面通过促进自噬与内质网应激诱导DTC细胞凋亡以及通过信号转导和转录活化因子3(signal transducer and activator oftranscription 3,STAT3)/细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)通路,抑制炎性反应、抑制肿瘤细胞能量代谢,抑制DTC细胞侵袭等有关。二甲双胝有望成为DTC治疗新的辅助治疗方法。

Metformin is a first-line drug in the treatment of diabetes.Recently,its anti-tumor effect has attracted wide attention.Some studies have found that the risk of differentiated thyroid cancer(DTC)is reduced in patients with type 2 diabetes taking metformin.The mechanisms may be associating with improving insulin resistance,regulating thyroid-stimulating hormone(TSH)and activating the AMP-activated protein kinase(AMPK)pathway to inhibit the proliferation of DTC cells;promoting autophagy and endoplasmic reticulum stress to induce apoptosis of DTC cells;inhibiting signal transduction and activator of transcription 3(STAT3)/extracellular signal-regulated kinase(ERK)pathway and inflammation,inhibiting energy metabolism of tumor cells to suppress DTC cell invasion.Metformin is expected to be a neoadjuvant therapy for DTC.