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Authors Zhang Y, Wang J, Wu D, Li M, Zhao F, Ren M, Cai Y, Dou J
Received 31 July 2017
Accepted for publication 16 February 2018
Published 10 April 2018 Volume 2018:11 Pages 2037—2050
DOI https://doi.org/10.2147/OTT.S147855
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 3
Editor who approved publication: Prof. Dr. Geoffrey Pietersz
Background: Epithelial
ovarian cancer (EOC) with insidious characteristic manifests no symptoms in its
early onset but most patients have advanced and distant cancer metastasis at
diagnosis. Innovative early diagnosis and effective treatment of EOC are
urgently needed.
Methods: In the study, we developed a novel agent of IL-21-secreting human
umbilical cord mesenchymal stem cells (hUCMSCs) combined with miR-200c to
evaluate its effects on SKOV3 EOC in vitro and in vivo.
Results: hUCMSCs-LV-IL-21 combined with miR-200c significantly inhibited
the SKOV3 cell mobility and tumorigenesis compared with hUCMSCs-LV-IL-21,
hUCMSCs- LV-vector, and hUCMSCs, respectively. These were reflected in
decreasing the tumor sizes and elongating the tumor bearing nude mouse
survival, accompanied with increasing the serum cytokine levels of IFN-γ, IL-21
and TNF-α as well as the splenocyte cytotoxicity. In addition, the expression
of β-catenin, cyclin-D1, Gli1, Gli2, and ZEB1 was decreased but the E-cadherin
expression was increased in tumor tissues of mice treated with hUCMSCs-LV-IL-21
plus miR-200c.
Conclusion: We demonstrated that the synergistic effect of fighting SKOV3 EOC
is attributable to repression of Wnt/β-catenin signaling and
epithelial-mesenchymal transition in SKOV3 EOC. The findings may provide a new
strategy for therapy of EOC.
Keywords: epithelial ovarian cancer, umbilical cord mesenchymal stem cells,
IL-21, miR-200c, Wnt/β-catenin signaling, epithelial–mesenchymal transition