二甲双胍抑制甲状腺乳头状癌的相关作用机制

The mechanisms of metformin inhibiting papillary thyroid carcinoma

甲状腺恶性肿瘤中最常见的病理类型是甲状腺乳头状癌(papillary thyroid carcinoma,PTC),其分化程度好,生长速度缓慢,恶性程度低,预后较好,但PTC的发病率却在全球范围内呈逐年增长趋势。目前临床上治疗PTC的主要方法包括手术切除及术后TSH抑制治疗等,由于常规治疗带来的并发症较多,严重影响患者的生存质量。因此寻找一种新方法治疗PTC意义重大。大量流行病学研究表明,二甲双胍不仅是临床上的一线降糖药物,而且还具有改善肿瘤预后的特点。目前研究显示二甲双胍抗PTC效应可能涉及多种机制,包括活化LKB1 AMPK、抑制mTOR信号通路,诱导细胞周期阻滞及细胞凋亡,抑制肿瘤坏死因子α诱导的CXCL8分泌,影响胰岛素/胰岛素样生长因子 1,抑制GLUT1和PKM2的表达,降低TSH水平等。但具体机制尚未形成统一定论,本文就二甲双胍抑制PTC相关作用机制作一综述。

Papillary thyroid carcinoma(PTC)is the most common pathological type of thyroid malignancies.It has good differentiation,slow growth,low malignancy and good prognosis,but has shown an ever- increasing worldwide.At present,the main treatments for PTC include surgical resection and postoperative TSH suppression and so on.Because of more complications caused by conventional treatment,the quality of life of patients is affected seriously.Therefore,it is great significance to find a new method for the treatment of PTC.A large number of epidemiological studies have shown that metformin is not only a clinical first-line hypoglycemic agent,but also can improve the prognosis of cancer.Current researches show that the antitumor effects of metformin may involve a variety of mechanisms,including activating LKB1-AMPK,inhibiting mTOR pathway,inducing the cell cycle arrest and apoptosis,inhibiting the secretion of CXCL8 induced by TNF-α,affecting the insulin/IGF1,inhibiting expressions of both GLUT1 and PKM2,reducing TSH level and so on.But the specific mechanism has not been formed.This review summarizes the anti-cancer mechanisms of metformin on the papillary thyroid carcinoma.