IL-21-secreting hUCMSCs combined with miR-200c inhibit tumor growth and metastasis via repression of Wnt/β-catenin signaling and epithelial-mesenchymal transition in epithelial ovarian cancer
Yunxia Zhang,1,2 Jing Wang,2 Di Wu,1 Miao Li,1 Fenshu Zhao,1 Mulan Ren,2 Yunlong Cai,2 Jun Dou1 1Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Department of Gynecology & Obstetrics, Zhongda Hospital...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Dove Medical Press
2018-04-01
|
Series: | OncoTargets and Therapy |
Subjects: | |
Online Access: | https://www.dovepress.com/il-21-secreting-hucmscs-combined-with-mir-200c-inhibit-tumor-growth-an-peer-reviewed-article-OTT |
id |
doaj-48c7e14c8c194d68b4fa6cf2eb6677da |
---|---|
record_format |
Article |
spelling |
doaj-48c7e14c8c194d68b4fa6cf2eb6677da2020-11-25T00:59:35ZengDove Medical PressOncoTargets and Therapy1178-69302018-04-01Volume 112037205037669IL-21-secreting hUCMSCs combined with miR-200c inhibit tumor growth and metastasis via repression of Wnt/β-catenin signaling and epithelial-mesenchymal transition in epithelial ovarian cancerZhang YWang JWu DLi MZhao FRen MCai YDou JYunxia Zhang,1,2 Jing Wang,2 Di Wu,1 Miao Li,1 Fenshu Zhao,1 Mulan Ren,2 Yunlong Cai,2 Jun Dou1 1Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Department of Gynecology & Obstetrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China 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 transitionhttps://www.dovepress.com/il-21-secreting-hucmscs-combined-with-mir-200c-inhibit-tumor-growth-an-peer-reviewed-article-OTTEpithelial ovarian cancerumbilical cord mesenchymal stem cellsIL-21miR-200cWnt/β-catenin signalingepithelial-mesenchymal transition |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhang Y Wang J Wu D Li M Zhao F Ren M Cai Y Dou J |
spellingShingle |
Zhang Y Wang J Wu D Li M Zhao F Ren M Cai Y Dou J IL-21-secreting hUCMSCs combined with miR-200c inhibit tumor growth and metastasis via repression of Wnt/β-catenin signaling and epithelial-mesenchymal transition in epithelial ovarian cancer OncoTargets and Therapy Epithelial ovarian cancer umbilical cord mesenchymal stem cells IL-21 miR-200c Wnt/β-catenin signaling epithelial-mesenchymal transition |
author_facet |
Zhang Y Wang J Wu D Li M Zhao F Ren M Cai Y Dou J |
author_sort |
Zhang Y |
title |
IL-21-secreting hUCMSCs combined with miR-200c inhibit tumor growth and metastasis via repression of Wnt/β-catenin signaling and epithelial-mesenchymal transition in epithelial ovarian cancer |
title_short |
IL-21-secreting hUCMSCs combined with miR-200c inhibit tumor growth and metastasis via repression of Wnt/β-catenin signaling and epithelial-mesenchymal transition in epithelial ovarian cancer |
title_full |
IL-21-secreting hUCMSCs combined with miR-200c inhibit tumor growth and metastasis via repression of Wnt/β-catenin signaling and epithelial-mesenchymal transition in epithelial ovarian cancer |
title_fullStr |
IL-21-secreting hUCMSCs combined with miR-200c inhibit tumor growth and metastasis via repression of Wnt/β-catenin signaling and epithelial-mesenchymal transition in epithelial ovarian cancer |
title_full_unstemmed |
IL-21-secreting hUCMSCs combined with miR-200c inhibit tumor growth and metastasis via repression of Wnt/β-catenin signaling and epithelial-mesenchymal transition in epithelial ovarian cancer |
title_sort |
il-21-secreting hucmscs combined with mir-200c inhibit tumor growth and metastasis via repression of wnt/β-catenin signaling and epithelial-mesenchymal transition in epithelial ovarian cancer |
publisher |
Dove Medical Press |
series |
OncoTargets and Therapy |
issn |
1178-6930 |
publishDate |
2018-04-01 |
description |
Yunxia Zhang,1,2 Jing Wang,2 Di Wu,1 Miao Li,1 Fenshu Zhao,1 Mulan Ren,2 Yunlong Cai,2 Jun Dou1 1Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Department of Gynecology & Obstetrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China 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 |
topic |
Epithelial ovarian cancer umbilical cord mesenchymal stem cells IL-21 miR-200c Wnt/β-catenin signaling epithelial-mesenchymal transition |
url |
https://www.dovepress.com/il-21-secreting-hucmscs-combined-with-mir-200c-inhibit-tumor-growth-an-peer-reviewed-article-OTT |
work_keys_str_mv |
AT zhangy il21secretinghucmscscombinedwithmir200cinhibittumorgrowthandmetastasisviarepressionofwntbetacateninsignalingandepithelialmesenchymaltransitioninepithelialovariancancer AT wangj il21secretinghucmscscombinedwithmir200cinhibittumorgrowthandmetastasisviarepressionofwntbetacateninsignalingandepithelialmesenchymaltransitioninepithelialovariancancer AT wud il21secretinghucmscscombinedwithmir200cinhibittumorgrowthandmetastasisviarepressionofwntbetacateninsignalingandepithelialmesenchymaltransitioninepithelialovariancancer AT lim il21secretinghucmscscombinedwithmir200cinhibittumorgrowthandmetastasisviarepressionofwntbetacateninsignalingandepithelialmesenchymaltransitioninepithelialovariancancer AT zhaof il21secretinghucmscscombinedwithmir200cinhibittumorgrowthandmetastasisviarepressionofwntbetacateninsignalingandepithelialmesenchymaltransitioninepithelialovariancancer AT renm il21secretinghucmscscombinedwithmir200cinhibittumorgrowthandmetastasisviarepressionofwntbetacateninsignalingandepithelialmesenchymaltransitioninepithelialovariancancer AT caiy il21secretinghucmscscombinedwithmir200cinhibittumorgrowthandmetastasisviarepressionofwntbetacateninsignalingandepithelialmesenchymaltransitioninepithelialovariancancer AT douj il21secretinghucmscscombinedwithmir200cinhibittumorgrowthandmetastasisviarepressionofwntbetacateninsignalingandepithelialmesenchymaltransitioninepithelialovariancancer |
_version_ |
1725217548614500352 |