Silencing of Livin inhibits tumorigenesis and metastasis via VEGF and MMPs pathway in lung cancer

  • Authors:
    • Xian Lin
    • Hong-Ru Li
    • Xiao-Fen Lin
    • Mei-E Yu
    • Xun-Wei Tu
    • Zhi-Dan Hua
    • Ming Lin
    • Neng-Luan Xu
    • Li-Li Han
    • Yu-Sheng Chen
  • View Affiliations

  • Published online on: June 19, 2015     https://doi.org/10.3892/ijo.2015.3058
  • Pages: 657-667
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Livin, an inhibitor of apoptosis protein (IAP), is overexpressed in various cancers and decreases tumor sensitivity to chemotherapy and radiotherapy. However, the effect of Livin on lung adenocarcinoma metastasis and the specific mechanism involved remain unclear. RNAi technology was used to stably silence Livin in A549 cells in the present study. The effect of Livin on tumor growth and invasion was investigated in lung cancer cells in vitro and animal models were established to determine the anti-metastasis ability of Livin silencing in vivo. The results indicated that Livin knock-down suppressed cell proliferation and inhibited cell invasion, accompanied by downregulation of VEGF and MMP-2/-9. Silencing of Livin resulted in the prevention of xenograft tumor formation. Seventy-five immunodeficient male BALB/C nude mice were randomly divided into three groups, the relative ratio of the areas with pulmonary nodules in the experimental group decreased from 46.71±7.27% to 11.07±2.94% compared with the negative control group (P<0.001), indicating the interaction between Livin, VEGF and MMPs. The xenograft tumor model of intravenous injection of tumor cells were successfully established and applied for the analysis of lung cancer tumorigenesis and metastasis in a time-dependent manner for the first time. Based on the reliable and reproducible animal model, our findings indicate that knock-down of Livin inhibits cell growth and invasion through blockade of the VEGF and MMPs pathways in lung cancer cells in vitro, and inhibits tumorigenesis and metastasis of lung cancer in vivo, suggesting that Livin is a promising antitumor target.
View Figures
View References

Related Articles

Journal Cover

August-2015
Volume 47 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Lin X, Li H, Lin X, Yu M, Tu X, Hua Z, Lin M, Xu N, Han L, Chen Y, Chen Y, et al: Silencing of Livin inhibits tumorigenesis and metastasis via VEGF and MMPs pathway in lung cancer. Int J Oncol 47: 657-667, 2015
APA
Lin, X., Li, H., Lin, X., Yu, M., Tu, X., Hua, Z. ... Chen, Y. (2015). Silencing of Livin inhibits tumorigenesis and metastasis via VEGF and MMPs pathway in lung cancer. International Journal of Oncology, 47, 657-667. https://doi.org/10.3892/ijo.2015.3058
MLA
Lin, X., Li, H., Lin, X., Yu, M., Tu, X., Hua, Z., Lin, M., Xu, N., Han, L., Chen, Y."Silencing of Livin inhibits tumorigenesis and metastasis via VEGF and MMPs pathway in lung cancer". International Journal of Oncology 47.2 (2015): 657-667.
Chicago
Lin, X., Li, H., Lin, X., Yu, M., Tu, X., Hua, Z., Lin, M., Xu, N., Han, L., Chen, Y."Silencing of Livin inhibits tumorigenesis and metastasis via VEGF and MMPs pathway in lung cancer". International Journal of Oncology 47, no. 2 (2015): 657-667. https://doi.org/10.3892/ijo.2015.3058