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

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...

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

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 Ras/MEK/ERK signaling pathways.