二磷酸腺苷核糖基化因子6对甲状腺乳头状癌细胞增殖和转移的影响  

Effects and mechanisms of ARF6 on proliferation and metastasis of papillary thyroid carcinoma cells

作　　者：席羽 周冬梅 赵锛活 安军 李伟 XI Yu;ZHOU Dongmei;ZHAO Benhuo;AN Jun;LI Wei(The First Clinical College of Xuzhou Medical University,Xuzhou,Jiangsu 221000,China;Department of Endocrinology,Affiliated Hospital of Xuzhou Medical University,Xuzhou,Ji-angsu 221000,China;Digestive Diseases Research Center,Xuzhou Medical University,Xu-zhou,Jiangsu 221000,China;Department of Endocrinology,The Third Medical Center of Chi-nese People's Liberation Army General Hospital,Beijing 100089,China)

机构地区：[1]徐州医科大学第一临床学院,江苏徐州221000 [2]徐州医科大学附属医院内分泌科,江苏徐州221000 [3]徐州医科大学消化病研究中心,江苏徐州221000 [4]解放军总医院第三医学中心内分泌科,北京100089

出　　处：《安徽医药》2022年第5期959-964,共6页Anhui Medical and Pharmaceutical Journal

摘　　要：目的探讨二磷酸腺苷核糖基化因子6(ARF6)对甲状腺乳头状癌细胞B-CPAP增殖和转移的影响及相关机制。方法在B-CPAP细胞中构建ARF6沉默细胞系及瞬时转染外源3×Flag-ARF6;利用EdU、CCK-8实验检测ARF6对B-CPAP细胞增殖的影响;利用Transwell实验检测ARF6对B-CPAP细胞转移的影响;利用蛋白质印迹法(Westernblotting)检测沉默及过表达ARF6对细胞外调节激酶1/2(ERK1/2)、上皮型钙黏蛋白(E-cadherin)及基质金属蛋白酶-9(MMP-9)蛋白表达的影响。结果与对照组相比,沉默ARF6后B-CPAP细胞的增殖、侵袭和迁移的能力明显下降[ARF6沉默组及其对照组EdU阳性细胞的比例分别为(33.75±1.50)%和(39.65±2.21)%,第5天OD值分别为(0.66±0.03)和(0.83±0.03),细胞侵袭数量分别为(614.66±18.52)和(898.34±38.94)个,细胞迁移数量分别为(588.67±18.02)和(922.32±34.91)个,均P<0.05]。与对照组相比,过表达ARF6后B-CPAP细胞的增殖、侵袭和迁移的能力明显提升[ARF6过表达组及其对照组EdU阳性细胞的比例分别为(46.53±4.09)%和(36.89±2.27)%,第5天OD值分别为(1.06±0.03)和(0.81±0.02),细胞侵袭数量分别为(943.68±24.69)和(758.42±10.78)个,细胞迁移数量分别为(974.68±23.68)和(726.32±27.04)个,均P<0.05]。沉默ARF6可上调B-CPAP细胞中p-ERK1/2和MMP-9的表达、下调E-cadherin的表达,过表达ARF6时则相反,均P<0.05。结论ARF6可能通过调控p-ERK1/2、MMP-9及E-cadherin的蛋白表达,从而促进甲状腺乳头状癌细胞B-CPAP的增殖和转移。Objective To investigate the effects of ADP-ribosylation factor 6(ARF6) on proliferation and metastasis of papillary thyroid carcinoma B-CPAP cells and its related mechanism.Methods ARF6 silencing cell line was constructed in B-CPAP cells and the exogenous 3×Flag-ARF6 was transiently transfected.The effects of ARF6 on proliferation of B-CPAP cells were measured by EdU and CCK-8 assays.The effects of ARF6 on metastasis of B-CPAP cells were measured by Trans well assays.Western blotting was used to detect the expression of ERK1/2,E-cadherin and MMP-9 while silencing and overexpressing ARF6.Results Compared with control group,silencing ARF6 expression significantly inhibited the proliferation,invasion and migration of papillary thyroid carcinoma BCPAP cells [the proportions of EdU positive cells of ARF6 silencing group and its control group were respectively(33.75±1.50) % and(39.65±2.21)%,the OD values of 5^(th) day were respectively(0.66±0.03) and(0.83±0.03),the numbers of cell invasion were respectively(614.66±18.52) and(898.34±38.94),the numbers of cell migration were respectively(588.67±18.02) and(922.32±34.91),all P<0.05].Compared with control group,over-expression of ARF6 significantly promoted the proliferation,invasion and migration of papillary thyroid carcinoma B-CPAP cells [the proportions of EdU positive cells of ARF6 over-expressing group and its control group were respectively(46.53±4.09)% and(36.89±2.27)%,the OD values of 5^(th) day were respectively(1.06±0.03) and(0.81±0.02),the numbers of cell invasion were respectively(943.68±24.69) and(758.42±10.78),the numbers of cell migration were respectively(974.68±23.68) and(726.32±27.04),all P<0.05].ARF6 positively regulated the expression of p-ERK1/2 and MMP-9 and negatively regulated the expression of E-cadherin,but the opposite was true when ARF6 was overexpressed,all P<0.05.Conclusion ARF6 may promote the proliferation and metastasis of papillary thyroid carcinoma B-CPAP cells by regulating the expression of p-ERK1/2,MMP-9 and E-cadheri

关 键 词：甲状腺肿瘤 癌 乳头状 二磷酸腺苷核糖基化因子6 细胞外调节激酶1/2 上皮型钙黏蛋白 基质金属蛋白酶-9 

分 类 号：R736.1[医药卫生—肿瘤]