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A novel uPAg-KPI fusion protein inhibits the growth and invasion of human ovarian cancer cells in vitro

  • Authors:
    • Li-Ping Zhao
    • Tian-Min Xu
    • Mu-Jie Kan
    • Ye-Chen Xiao
    • Man-Hua Cui
  • View Affiliations / Copyright

    Affiliations: Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China, Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Jilin University, Changchun, Jilin 130021, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1310-1316
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    Published online on: March 24, 2016
       https://doi.org/10.3892/ijmm.2016.2540
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Abstract

Urokinase-type plasminogen activator (uPA) acts by breaking down the basement membrane and is involved in cell proliferation, migration and invasion. These actions are mediated by binding to the uPA receptor (uPAR) via its growth factor domain (GFD). The present study evaluated the effects of uPAg-KPI, a fusion protein of uPA-GFD and a kunitz protease inhibitor (KPI) domain that is present in the amyloid β-protein precursor. Using SKOV-3 cells, an ovarian cancer cell line, we examined cell viability, migration, invasion and also protein expression. Furthermore, we examined wound healing, and migration and invasion using a Transwell assay. Our data showed that uPAg-KPI treatment reduced the viability of ovarian cancer SKOV-3 cells in both a concentration and time-dependent manner by arresting tumor cells at G1/G0 phase of the cell cycle. The IC50 of uPAg-KPI was 0.5 µg/µl after 48 h treatment. At this concentration, uPAg-KPI also inhibited tumor cell colony formation, wound closure, as well as cell migration and invasion capacity. At the protein level, western blot analysis demonstrated that uPAg-KPI exerted no significant effect on the expression of total extracellular signal-regulated kinase (ERK)1/ERK2 and AKT, whereas it suppressed levels of phosphorylated ERK1/ERK2 and AKT. Thus, we suggest that this novel uPAg-KPI fusion protein reduced cell viability, colony formation, wound healing and the invasive ability of human ovarian cancer SKOV-3 cells in vitro by regulating ERK and AKT signaling. Further studies using other cell lines will confirm these findings.
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Copy and paste a formatted citation
Spandidos Publications style
Zhao L, Xu T, Kan M, Xiao Y and Cui M: A novel uPAg-KPI fusion protein inhibits the growth and invasion of human ovarian cancer cells in vitro. Int J Mol Med 37: 1310-1316, 2016.
APA
Zhao, L., Xu, T., Kan, M., Xiao, Y., & Cui, M. (2016). A novel uPAg-KPI fusion protein inhibits the growth and invasion of human ovarian cancer cells in vitro. International Journal of Molecular Medicine, 37, 1310-1316. https://doi.org/10.3892/ijmm.2016.2540
MLA
Zhao, L., Xu, T., Kan, M., Xiao, Y., Cui, M."A novel uPAg-KPI fusion protein inhibits the growth and invasion of human ovarian cancer cells in vitro". International Journal of Molecular Medicine 37.5 (2016): 1310-1316.
Chicago
Zhao, L., Xu, T., Kan, M., Xiao, Y., Cui, M."A novel uPAg-KPI fusion protein inhibits the growth and invasion of human ovarian cancer cells in vitro". International Journal of Molecular Medicine 37, no. 5 (2016): 1310-1316. https://doi.org/10.3892/ijmm.2016.2540
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao L, Xu T, Kan M, Xiao Y and Cui M: A novel uPAg-KPI fusion protein inhibits the growth and invasion of human ovarian cancer cells in vitro. Int J Mol Med 37: 1310-1316, 2016.
APA
Zhao, L., Xu, T., Kan, M., Xiao, Y., & Cui, M. (2016). A novel uPAg-KPI fusion protein inhibits the growth and invasion of human ovarian cancer cells in vitro. International Journal of Molecular Medicine, 37, 1310-1316. https://doi.org/10.3892/ijmm.2016.2540
MLA
Zhao, L., Xu, T., Kan, M., Xiao, Y., Cui, M."A novel uPAg-KPI fusion protein inhibits the growth and invasion of human ovarian cancer cells in vitro". International Journal of Molecular Medicine 37.5 (2016): 1310-1316.
Chicago
Zhao, L., Xu, T., Kan, M., Xiao, Y., Cui, M."A novel uPAg-KPI fusion protein inhibits the growth and invasion of human ovarian cancer cells in vitro". International Journal of Molecular Medicine 37, no. 5 (2016): 1310-1316. https://doi.org/10.3892/ijmm.2016.2540
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