ADAMDEC1通过Wnt/β-catenin信号通路调控胰腺癌细胞的生长和转移  

ADAMDEC1 regulates growth and migration of pancreatic carcinoma cells through Wnt/β-catenin signaling pathway

作　　者：黄小勇[1] 樊心悦 徐向荣 蔺晓银 刘雨思 史海燕[1] 杜娟[1] 景红梅 HUANG Xiaoyong;FAN Xinyue;XU Xiangrong;LIN Xiaoyin;LIU Yusi;SHI Haiyan;DU Juan;JING Hongmei(Medical College of Yan'an University,Yan'an 716000,China;Yan'an Baota District People's Hospital,Yan'an 716000,China;Yan'an People's Hospital,Yan'an 716000,China)

机构地区：[1]延安大学医学院,陕西延安716000 [2]延安市宝塔区人民医院,陕西延安716000 [3]延安市人民医院,陕西延安716000

出　　处：《中国病理生理杂志》2024年第8期1369-1377,共9页Chinese Journal of Pathophysiology

基　　金：延安市重点研发计划项目(No.2022SLSFGG-051)。

摘　　要：目的:探究敲减解整联蛋白及金属蛋白酶(a disintegrin and metalloproteinase,ADAM)结构域样癸蛋白1(ADAM domain-like decysin 1,ADAMDEC1)对胰腺癌细胞增殖、迁移和侵袭能力的影响。方法:利用GEPIA和UALCAN在线数据库对ADAMDEC1在胰腺癌组织中的表达情况进行分析。Western blot检测人胰腺癌细胞系(MIA PaCa-2和PANC-1)和胰腺导管细胞系(hTERT-HPNE)中ADAMDEC1的蛋白表达水平。采用CCK-8实验、集落形成实验、细胞划痕实验和Transwell实验检测敲减ADAMDEC1对胰腺癌细胞增殖、迁移和侵袭能力的影响;Western blot检测敲减ADAMDEC1对胰腺癌细胞中迁移、侵袭及Wnt/β-catenin信号通路相关蛋白表达水平的影响。此外,通过恢复性实验,检测Wnt/β-catenin信号通路激动剂CHIR-99021对敲减ADAMDEC1抑制胰腺癌细胞生长和转移作用的影响。结果:(1)ADAMDEC1在胰腺癌中高表达;(2)敲减ADAMDEC1表达后,胰腺癌细胞增殖、迁移和侵袭能力显著下降;(3)敲减ADAMDEC1后,E-cadherin蛋白表达增加,而基质金属蛋白酶9、N-cadherin和vimentin蛋白表达减少,Wnt/β-catenin信号通路相关蛋白表达亦减少;(4)CHIR-99021与ADAMDEC1小干扰RNA共处理胰腺癌细胞,可逆转敲减ADAMDEC1对胰腺癌细胞增殖、迁移和侵袭能力的抑制作用。结论:ADAMDEC1在胰腺癌中高表达,可通过Wnt/β-catenin信号通路调控胰腺癌细胞的增殖、迁移和侵袭。AIM:To investigate the effect of a disintegrin and metalloproteinase(ADAM)domain-like decysin 1(ADAMDEC1)knockdown on the proliferation,migration and invasion of pancreatic carcinoma cells.METHODS:Expression levels of ADAMDEC1 in pancreatic carcinoma tissues were analyzed using the GEPIA and UALCAN online databases.Western blot analysis was employed to detect the protein expression levels of ADAMDEC1 in pancreatic carcinoma cell lines(MIA PaCa-2 and PANC-1)and pancreatic ductal cell line(hTERT-HPNE).The effects of ADAMDEC1 knockdown on cell proliferation,migration and invasion were evaluated using CCK-8,colony formation,wound-healing and Transwell assays.Additionally,Western blot analysis was used to detect the effects of ADAMDEC1 knockdown on the expression levels of migration and invasion markers,as well as Wnt/β-catenin signaling pathway-related proteins in pancreatic carcinoma cells.Furthermore,a recovery experiment was conducted to assess the role of Wnt/β-catenin signaling pathway agonist CHIR-99021 in ADAMDEC1 knockdown-induced inhibition of pancreatic carcinoma cell growth and migration.RESULTS:(1)ADAMDEC1 was highly expressed in pancreatic carcinoma cells.(2)Knockdown of ADAMDEC1 led to a significant reduction in the proliferation,migration and invasion of pancreatic carcinoma cells.(3)Knockdown of ADAMDEC1 resulted in increased E-cadherin protein expression and decreased levels of matrix metalloproteinase 9,Ncadherin and vimentin proteins,alongside a reduction in the expression of Wnt/β-catenin signaling pathway-related proteins.(4)Co-treatment of pancreatic carcinoma cells with CHIR-99021 and ADAMDEC1 small interfering RNA reversed the inhibitory effects of ADAMDEC1 knockdown on cell proliferation,migration,and invasion.CONCLUSION:ADAMDEC1 is highly expressed in pancreatic carcinoma.Targeted silencing of ADAMDEC1 has the potential to inhibit the proliferation,migration and invasion of pancreatic carcinoma cells by regulating the Wnt/β-catenin signaling pathway.

关 键 词：胰腺癌 ADAMDEC1蛋白 细胞增殖 细胞迁移 细胞侵袭 WNT/Β-CATENIN信号通路 

分 类 号：R735.9[医药卫生—肿瘤] R363.2[医药卫生—临床医学] Q279[生物学—细胞生物学]