Rab11a通过PI3K/AKT和Ras/MEK/ERK信号通路调节胰腺癌细胞凋亡和侵袭  

Rab11a Regulates Apoptosis and Invasion of Pancreatic Cancer Cells via PI3K/AKT and Ras/MEK/ERK Signaling Pathways

作　　者：王云[1] 朱星枚[2] 罗玉梅 王小云 和水祥[1] WANG Yun;ZHU Xing-mei;LUO Yu-mei;WANG Xiao-yun;HE Shui-xiang(Department of Gastroenterology,The First Affiliated Hospital of Xi’an Jiaotong University,Xi'an,Shanxi,710061,China;College of Pharmacy,Shanxi University of Chinese Medicine,Xianyang,Shanxi,712046,China;Department of Infectious,The First Affiliated Hospital of Xi’an Jiaotong University,Shanxi,710061,China)

机构地区：[1]西安交通大学第一附属医院消化内科,陕西西安710061 [2]陕西中医药大学药学院,陕西咸阳712046 [3]西安交通大学第一附属医院感染科,陕西西安710061

出　　处：《现代生物医学进展》2021年第5期811-818,共8页Progress in Modern Biomedicine

基　　金：国家自然科学基金青年基金项目(81402186);陕西省重点研发计划项目(2016SF-183)。

摘　　要：目的:探究Rab11a在胰腺癌中的表达模式及其对肿瘤生长和转移的影响。方法:通过免疫组织化学法、RT-PCR和Western blot检测60例胰腺癌患者的癌组织和癌旁组织中Rab11a的表达。通过对人胰腺癌细胞系PANC1转染靶向Rab11a的小干扰RNA或过表达Rab11a的pcDNA3.1质粒考察Rab11a对细胞增殖、凋亡、迁移和侵袭的影响。通过Western blot检测PANC1细胞中PI3K、AKT、Ras、MEK、ERK1/2和GSK3β的磷酸化水平。结果:胰腺癌组织中Rab11a的表达水平均高于癌旁组织(P<0.05)。Rab11a的表达水平与TNM分期和淋巴结转移有关(P<0.05)。CCK-8测试和细胞集落形成实验显示,下调Rab11a抑制了PANC1细胞的增殖(P<0.05)。流式细胞术显示,下调Rab11a促进了PANC1细胞的凋亡(P<0.05)。细胞划痕实验显示,下调Rab11a抑制了PANC1细胞的迁移能力(P<0.05)。Matrigel Transwell实验显示,下调Rab11a抑制了PANC1细胞的侵袭能力(P<0.05)。然而,上调Rab11a则促进了PANC1细胞的增殖、迁移和侵袭,并抑制了细胞凋亡(P<0.05)。蛋白质印迹分析显示,下调Rab11a抑制了PANC1细胞中PI3K/AKT和Ras/MEK/ERK信号通路的活化(P<0.05)。此外,应用PI3K/AKT和Ras/MEK/ERK信号通路的选择性抑制剂处理PANC1细胞可阻断Rab11a对细胞增殖的促进作用(P<0.05)。结论:Rab11a的高表达是胰腺癌预后恶化的潜在生物标志物。靶向抑制Rab11a可通过抑制PI3K/AKT和Ras/MEK/ERK信号通路来降低胰腺癌的生长和转移能力。Objective:To investigate the expression pattern of Rab11 a in pancreatic cancer and its effect on tumor growth and metastasis.Methods:Immunohistochemistry,RT-PCR and Western blot were used to detect the expression of Rab11 a in cancer tissues and adjacent tissues of 60 patients with pancreatic cancer.The human pancreatic cancer cell line PANC1 was transfected with small interfering RNA targeting Rab11 a or pcDNA3.1 plasmid overexpressing Rab11 a to investigate the effects of Rab11 a on cell proliferation,apoptosis,migration and invasion.The phosphorylation levels of PI3 K,AKT,Ras,MEK,ERK1/2 and GSK3βin PANC1 cells were detected by Western blot.Results:The expression level of Rab11 a in pancreatic cancer tissues was higher than that in adjacent tissues(P<0.05).The expression level of Rab11 a was related to TNM stage and lymph node metastasis(P<0.05).CCK-8 test and cell colony formation experiment showed that down-regulation of Rab11 a inhibited the proliferation of PANC1 cells(P<0.05).Flow cytometry showed that down-regulation of Rab11 a promoted the apoptosis of PANC1 cells(P<0.05).The wound healing experiment showed that down-regulation of Rab11 a inhibited the migration ability of PANC1 cells(P<0.05).Matrigel Transwell experiments showed that down-regulation of Rab11 a inhibited the invasion ability of PANC1 cells(P<0.05).However,up-regulation of Rab11 a promoted the proliferation,migration and invasion and inhibited apoptosis in PANC1 cells(P<0.05).Western blot analysis showed that down-regulation of Rab11 a inhibited the activation of PI3 K/AKT and Ras/MEK/ERK signaling pathways in PANC1 cells(P<0.05).In addition,treatment of PANC1 cells with selective inhibitors of PI3 K/AKT and Ras/MEK/ERK signaling pathways can block Rab11 a’s promotion of cell proliferation(P<0.05).Conclusion:The high expression of Rab11 a is a potential biomarker for the worsening prognosis of pancreatic cancer.Targeted inhibition of Rab11 a can reduce the growth and metastatic ability of pancreatic cancer by inhibiting PI3 K/AKT and

关 键 词：Rab11a 胰腺癌 淋巴结转移 PI3K/AKT信号通路 Ras/MEK/ERK信号通路 

分 类 号：R-33[医药卫生] R735.9