乐伐替尼靶向调节VEGFR/PI3K/AKT治疗晚期甲状腺癌的作用机制  

The Mechanism of Action of Lenvatinib in the Regulation of VEGFR/PI3K/AKT in the Treatment of Advanced Thyroid Cancer

作　　者：王宁[1] 刘金彪[1] WANG Ning;LIU Jinbiao(The First Affiliated Hospital of Henan University of Science and Technology,Luoyang,471003)

机构地区：[1]河南科技大学第一附属医院,471003

出　　处：《实用癌症杂志》2021年第3期415-418,422,共5页The Practical Journal of Cancer

基　　金：河南省自然科学基金项目(编号:4162300410045)。

摘　　要：目的探讨乐伐替尼靶向调节VEGFR/PI3K/AKT治疗晚期甲状腺癌的作用机制。方法选取100例晚期分化型甲状腺癌患者,采用口服乐伐替尼,剂量为24 mg/d,直到出现无法耐受的副作用和疾病恶化。评价药物使用疗效;观察患者甲状腺癌血清标志物Tg水平变化;采用免疫组织化学法检测甲状腺癌患者癌组织中VEGFR2蛋白的表达;采用Western Blot法和Real-Time PCR法检测甲状腺癌癌组织中PI3K、AKT的磷酸化蛋白和基因水平;采用Caspase 3试剂盒测定凋亡蛋白Caspase 3表达。结果乐伐替尼治疗晚期分化型甲状腺癌的有效率为60.00%,患者血清TgAb浓度较治疗前明显下降(P<0.05)。与癌旁组织相比,甲状腺癌组织内Caspase 3活性、VEGFR2蛋白表达含量、p-PI3K和p-AKT蛋白含量及PI3K和AKT mRNA表达明显上升(P<0.05)。晚期分化型甲状腺癌患者应用乐伐替尼治疗后,Caspase 3活性、VEGFR2蛋白表达含量、p-PI3K和p-AKT蛋白含量及PI3K和AKT mRNA表达较治疗前显著降低,差异具有统计学意义(P<0.05)。结论乐伐替尼可以有效治疗晚期分化型甲状腺癌,并调控VEGFR靶向途径抑制PI3K/AKT信号通路,诱导甲状腺癌细胞凋亡。Objective To investigate the mechanism of Lenvatinib targeting VEGFR/PI3K/Akt in the treatment of advanced thyroid cancer.Methods 100 patients with advanced differentiated thyroid cancer were treated with oral lenvatinib at a dose of 24 mg/D until intolerable side effects and disease progression occurred.To evaluate the efficacy of drug use;to observe the changes of serum marker Tg of patients with thyroid cancer;to detect the expression of VEGFR2 protein in thyroid cancer tissues by immunohistochemistry;to detect the phosphorylated protein and gene levels of PI3K and Akt in thyroid cancer tissues by Western blot and real time PCR;to detect the expression of apoptotic protein caspase 3 by caspase 3 kit.Results The effective rate of lenvatinib in the treatment of advanced differentiated thyroid cancer was 60.00%,and the serum TGAb concentration was significantly lower than that before treatment(P<0.05).Compared with the adjacent tissues,the activity of caspase 3,the expression of VEGFR2,the protein contents of p-pi3k and p-Akt,and the mRNA expressions of PI3K and Akt in thyroid carcinoma tissues were significantly increased(P<0.05).The caspase-3 activity,VEGFR2 protein expression,p-pi3k and p-Akt protein content and PI3K and Akt mRNA expression in patients with advanced differentiated thyroid cancer were significantly lower than those before treatment(P<0.05).Conclusion Lenvatinib can effectively treat advanced differentiated thyroid cancer,regulate VEGFR targeting pathway,inhibit PI3K/Akt signaling pathway,and induce apoptosis of thyroid cancer cells.

关 键 词：晚期分化型甲状腺 乐伐替尼 VEGFR PI3K AKT 

分 类 号：R736.1[医药卫生—肿瘤]