白细胞介素-11促进甲状腺未分化癌侵袭转移的机制  

Study on the mechanism of interleukine-11 promoting anaplastic thyroid carcinoma cells invasion and metastasis

作　　者：钟兆铭 王伟[1] 齐潇 罗娟章 王士琪 程瑞[1] 刘婷[1] 秦汝佳 赵再礼 梁进 孙传政[1] Zhong Zhaoming;Wang Wei;Qi Xiao;Luo Juanzhang;Wang Shiqi;Cheng Rui;Liu Ting;Qin Rujia;Zhao Zaili;Liang Jin;Sun Chuanzheng(Department of Head and Neck Surgery Section Ⅱ, the Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China;Department of Medical Oncology, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China)

机构地区：[1]昆明医科大学第三附属医院云南省肿瘤医院头颈外二科,650118 [2]昆明医科大学第一附属医院肿瘤内科,650032

出　　处：《中华实验外科杂志》2019年第4期629-631,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目(81560470、81773127);云南省科技厅-昆医应用基础研究联合专项(2018FE001-058/246).

摘　　要：目的探讨低氧诱导甲状腺未分化癌(ATC)细胞分泌白细胞介素(IL)-11,后者促进ATC细胞侵袭和迁移能力的机制。方法敲低ATC细胞IL-11、缺氧诱导因子(HIF)-1α表达或用氯化钴、重组人白细胞介素(rhIL)-11、IL-11抗体处理ATC细胞,采用酶联免疫吸附试验(ELISA)检测细胞上清IL-11蛋白表达、实时荧光定量聚合酶链反应(Real-time PCR)和Western blot检测细胞IL-11 mRNA和蛋白表达、Transwell实验检测细胞侵袭和迁移能力,探索低氧诱导ATC细胞侵袭和迁移能力增强的机制。结果氯化钴刺激ATC细胞上调IL-11蛋白质及mRNA的表达。敲低HIF-1α组细胞侵袭实验跨膜数目[(61.7±4.9、30.0±4.6)个]少于对照组[(261.7±8.7)个,P<0.01],迁移实验跨膜数目[(87.3±4.5、73.8±5.4)个]少于对照组[(337.3±7.1)个,P<0.01]。rhIL-11处理ATC细胞后,磷酸化蛋白激酶B(p-Akt),磷酸化糖原合酶激酶-3β(p-GSK3β),Snail蛋白表达明显升高,而敲低ATC细胞IL-11表达后,p-Akt、p-GSK3β、Snail蛋白的表达明显降低。结论低氧环境通过HIF-1α介导上调IL-11表达诱导ATC细胞发生上皮-间充质转化,进而促进ATC细胞侵袭与迁移能力。Objective To explore the mechanism of hypoxia inducing interleukine (IL)-11 secretion in anaplastic thyroid carcinoma (ATC) cells and the mechanism of IL-11 promoting epithelial mesenchymal transition of ATC cells. Methods Knockdown of IL-11, hypoxia-inducible factor (HIF)-1α in ATC cells or treatment of ATC cells with Cobalt Chloride, recombinant human interleukin (rhIL)-11, IL-11 antibody, then the effects of these interventions on the invasion and migration ability of ATC cells and its mechanism were detected by enzyme-linked immunosorbent assay (ELISA), Transwell, Real-time polymerase chain reaction (PCR), Western blotting. Results Under treatment with Cobalt Chloride, the protein and mRNA expression of IL-11 increased in ATC cells. The number of invasive cells in the knockdown HIF-1α group (61.7±4.9, 30.0±4.6) was less than that of the control group 261.7±8.7 (P<0.01), and the number of migrated cells (87.3±4.5, 73.8±5.4) was less than the control group 337.3±7.1 (P<0.01). The expression ofphosphorylated Akt (p-Akt), phosphorylated glycogen synthase kinase 3β(p-GSK3β) and Snail protein was significantly increased after treatment with rhIL-11. The protein expression of p-Akt, p-GSK3β and Snail were significantly decreased after knockdown of IL-11 expression in ATC cells. Conclusion Hypoxia induced epithelial mesenchymal transition of ATC cells is the main mechanism of high invasion and migration of ATC cells.

关 键 词：甲状腺未分化癌 白细胞介素-11 上皮-间充质转化 侵袭与转移 

分 类 号：R736.1[医药卫生—肿瘤]