已发表论文

IL-21 分泌型 hUCMSC 与 miR-200c 结合通过阻抑上皮卵巢癌中的 Wnt/β-连环蛋白信号传导和上皮 - 间质转化来抑制肿瘤生长和转移

 

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