首页|NEDD4-1调控JAK2/STAT3通路参与胰腺癌发生、发展的研究

NEDD4-1调控JAK2/STAT3通路参与胰腺癌发生、发展的研究

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目的 探讨神经前体细胞表达发育下调蛋白 4-1(neural precursor cell expressed,developmentally down-regulated 4-1,NEDD4-1)在胰腺癌组织及细胞发生、发展过程中的作用及相关机制.方法 采用免疫组织化学法分析 NEDD4-1 在胰腺导管腺癌及癌旁组织中的表达差异;Western blot法检测 NEDD4-1 在胰腺癌细胞与正常胰腺导管上皮细胞内的表达改变;利用 siRNA沉默人胰腺癌 PANC-1 细胞中的 NEDD4-1 表达,检测细胞的生长增殖活力、凋亡率及迁移活性的改变,并探讨沉默前后细胞内 NEDD4-1、p-JAK2 及 p-STAT3 蛋白的表达变化.结果 胰腺导管腺癌组织中的 NEDD4-1 表达水平较癌旁组织显著上调(P<0.01);胰腺癌细胞株内的 NEDD4-1 蛋白表达水平较正常胰腺导管上皮细胞明显升高(P<0.01);转染 36h后,siNEDD4-1 组 NEDD4-1 蛋白表达水平仅为 siNC组的 41.71%±4.58%,组间比较差异有统计学意义(P<0.01);与 siNC组比较,siNEDD4-1 组 PANC-1 细胞生长增殖活性下降、凋亡率上升、迁移活力降低,且细胞内 NEDD4-1、p-JAK2 及 p-STAT3 蛋白表达水平明显下调(P<0.05).结论 NEDD4-1 在胰腺癌组织中及细胞中表达升高.沉默 NEDD4-1 可能通过调控 JAK2/STAT3 通路抑制胰腺癌细胞的增殖活性及迁移能力并诱导细胞凋亡.NEDD4-1 可能成为治疗胰腺癌的一个新靶点.
NEDD4-1 is Involved in the Occurrence and Development of Pancreatic Cancer by Regulating the JAK2/STAT3Pathway
Objective To investigate the role and mechanism of neural precursor cell expressed,developmentally down-regulated 4-1(NEDD4-1)in the occurrence and development of pancreatic cancer tissue and cell.Methods The expression of NEDD4-1 in pancreatic ductal adenocarcinoma and its adjacent tissues was detected by immunohistochemistry.The expression of NEDD4-1 in pancre-atic cancer cells and normal pancreatic ductal epithelial cells was detected by Western blot.The expression of NEDD4-1 in human pan-creatic carcinoma PANC-1 cells was silenced by siRNA,and the changes of growth,proliferation,apoptosis and migration activity were detected,and the changes of NEDD4-1,p-JAK2 and p-STAT3 protein expression in the cells before and after silencing were investi-gated.Results The expression level of NEDD4-1 in pancreatic ductal adenocarcinoma was significantly higher than that in adjacent tis-sues(P<0.01).The expression level of NEDD4-1 protein in pancreatic cancer cells was also significantly higher than that in normal pancreatic ductal epithelial cells(P<0.01).The expression level of NEDD4-1 protein in siNEDD4-1 group was only 41.71%±4.58%of that in siNC group at 36h after transfection,and the difference between two groups was statistically significant(P<0.01).Compared with siNC group,the growth and proliferation activity of PANC-1 cells in siNEDD4-1 group was decreased,while the apopto-sis rate was increased,and the protein expressions of NEDD4-1,p-JAK2 and p-STAT3 were significantly down-regulated(P<0.05).Conclusion The expression of NEDD4-1 is increased in pancreatic cancer tissues and cells.Silencing of NEDD4-1 may in-hibit the proliferation and migration activity of pancreatic cancer cells and induce cell apoptosis by regulating JAK2/STAT3 pathway.NEDD4-1may be a new target for the treatment of pancreatic cancer.

Pancreatic cancerNEDD4-1SilencingProgressionTarget

刘岩、张嫚嫚、毕亭亭

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221006 徐州市中心医院普外科、徐州医科大学徐州临床学院

221006 徐州市中心医院消化内科、徐州医科大学徐州临床学院

胰腺癌 NEDD4-1 沉默 进展 靶点

江苏省徐州市卫生健康委医学科技创新项目江苏省徐州医科大学附属医院优秀人才基金

XWKYHT20230051XYFY202201

2024

医学研究杂志
中国医学科学院

医学研究杂志

CSTPCD
影响因子:0.702
ISSN:1673-548X
年,卷(期):2024.53(4)
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