| 王 云,朱星枚,罗玉梅,王小云,和水祥.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[J].现代生物医学进展英文版,2021,(5):811-818. |
| 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 |
| Received:June 30, 2020 Revised:July 26, 2020 |
| DOI：10.13241/j.cnki.pmb.2021.05.003 |
| 中文关键词: Rab11a 胰腺癌 淋巴结转移 PI3K/AKT信号通路 Ras/MEK/ERK信号通路 |
| 英文关键词: Rab11a Pancreatic cancer Lymph node metastasis PI3K/AKT signaling pathway Ras/MEK/ERK signaling pathway |
| 基金项目: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） |
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| 中文摘要: |
| 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。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the expression pattern of Rab11a 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 Rab11a 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 Rab11a or pcDNA3.1 plasmid overexpressing Rab11a to investigate the effects of Rab11a on cell proliferation, apoptosis, migration and invasion. The phosphorylation levels of PI3K, AKT, Ras, MEK, ERK1/2 and GSK3β in PANC1 cells were detected by Western blot. Results: The expression level of Rab11a in pancreatic cancer tissues was higher than that in adjacent tissues (P<0.05). The expression level of Rab11a 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 Rab11a inhibited the proliferation of PANC1 cells (P<0.05). Flow cytometry showed that down-regulation of Rab11a promoted the apoptosis of PANC1 cells (P<0.05). The wound healing experiment showed that down-regulation of Rab11a inhibited the migration ability of PANC1 cells (P<0.05). Matrigel Transwell experiments showed that down-regulation of Rab11a inhibited the invasion ability of PANC1 cells (P<0.05). However, up-regulation of Rab11a promoted the proliferation, migration and invasion and inhibited apoptosis in PANC1 cells (P<0.05). Western blot analysis showed that down-regulation of Rab11a inhibited the activation of PI3K/AKT and Ras/MEK/ERK signaling pathways in PANC1 cells (P<0.05). In addition, treatment of PANC1 cells with selective inhibitors of PI3K/AKT and Ras/MEK/ERK signaling pathways can block Rab11a's promotion of cell proliferation (P<0.05). Conclusion: The high expression of Rab11a is a potential biomarker for the worsening prognosis of pancreatic cancer. Targeted inhibition of Rab11a can reduce the growth and metastatic ability of pancreatic cancer by inhibiting PI3K/AKT and Ras/MEK/ERK signaling pathways. |
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