title: Mechanism of Wnt/β-catenin signaling pathway in enhanced malignant phenotype of non-small cell lung cancer induced by anti-angiogenesis therapy.
abstract: OBJECTIVE
  To study the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of A549 cells of human non-small cell lung cancer induced by the anti-angiogenesis therapy.
  
  
  METHODS
  The siRNA technique was employed to inhibit the expression of vascular endothelial growth factor (VEGF) in A549 cells and simulate the clinical course of anti-angiogenesis therapy. Real-time PCR and western blot were used to study the change in the expression of Wnt/β-catenin signaling molecules at the mRNA and protein level respectively, as well as the effect on the epithelial mesenchymal transition in A549 cells. The proliferation and invasion abilities of tumor cells were detected to discuss the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of non-small cell lung cancer induced by the anti-angiogenesis therapy.
  
  
  RESULTS
  The specific siRNA could significantly inhibit the expression of VEGF in cells to simulate the anti-angiogenesis therapy. Under the action of 50 nM VEGF siRNA, the proliferation ability of A549 significantly increased (P < 0.05). After being treated with VEGF siRNA, the invasion ability of cells increased. Twenty-four hours after the transcription of 50 nM siRNA into cells, the number of cells that come through the membrane was 278.3 ± 12.9. Compared with the Ctrl siRNA group, when VEGF was inhibited, the expression of β-catenin and Cyclin D1 increased by 86% and 55% respectively. Meanwhile, the expression of E-cadherin decreased, while the one of vimentin increased.
  
  
  CONCLUSIONS
  siRNA can significantly inhibit the expression of VEGF. For the anti-angiogenesis therapy, the inhibited expression of VEGF can activate the Wnt/β-catenin signaling pathway to cause the epithelial mesenchymal transition and then the enhanced malignant phenotype of non-small cell lung cancer.
authors: Shandong University School of Medicine, Qingdao, Shandong 250000, China.
authors: Xiao-Xue
authors: XX
authors: Zhang
authors: Department of Oncology, Binzhou People's Hospital, Binzhou, Shandong 256610, China.
authors: Ling-Ling
authors: LL
authors: Zhang
authors: Department of Oncology, Binzhou People's Hospital, Binzhou, Shandong 256610, China.
authors: Huan-Lian
authors: HL
authors: Yang
authors: Department of Oncology, Qilu Hospital of Shandong University, Ji'nan, Shandong 250000, China. Electronic address: sdmzc0518@163.com.
authors: Xiu-Wen
authors: XW
authors: Wang
keywords: Anti-angiogenesis; Epithelial mesenchymal transition; Proliferation and invasion; Wnt1; β-Catenin