PMID- 29692616 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220317 IS - 1178-6930 (Print) IS - 1178-6930 (Electronic) IS - 1178-6930 (Linking) VI - 11 DP - 2018 TI - IL-21-secreting hUCMSCs combined with miR-200c inhibit tumor growth and metastasis via repression of Wnt/beta-catenin signaling and epithelial-mesenchymal transition in epithelial ovarian cancer. PG - 2037-2050 LID - 10.2147/OTT.S147855 [doi] AB - 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-gamma, IL-21 and TNF-alpha as well as the splenocyte cytotoxicity. In addition, the expression of beta-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/beta-catenin signaling and epithelial-mesenchymal transition in SKOV3 EOC. The findings may provide a new strategy for therapy of EOC. FAU - Zhang, Yunxia AU - Zhang Y AD - Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, People's Republic of China. AD - Department of Gynecology & Obstetrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People's Republic of China. FAU - Wang, Jing AU - Wang J AD - Department of Gynecology & Obstetrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People's Republic of China. FAU - Wu, Di AU - Wu D AD - Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, People's Republic of China. FAU - Li, Miao AU - Li M AD - Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, People's Republic of China. FAU - Zhao, Fenshu AU - Zhao F AD - Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, People's Republic of China. FAU - Ren, Mulan AU - Ren M AD - Department of Gynecology & Obstetrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People's Republic of China. FAU - Cai, Yunlong AU - Cai Y AD - Department of Gynecology & Obstetrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People's Republic of China. FAU - Dou, Jun AU - Dou J AD - Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, People's Republic of China. LA - eng PT - Journal Article DEP - 20180410 PL - New Zealand TA - Onco Targets Ther JT - OncoTargets and therapy JID - 101514322 PMC - PMC5901132 OTO - NOTNLM OT - IL-21 OT - Wnt/beta-catenin signaling OT - epithelial ovarian cancer OT - epithelial-mesenchymal transition OT - miR-200c OT - umbilical cord mesenchymal stem cells COIS- Disclosure The authors report no conflicts of interest in this work. EDAT- 2018/04/26 06:00 MHDA- 2018/04/26 06:01 PMCR- 2018/04/10 CRDT- 2018/04/26 06:00 PHST- 2018/04/26 06:00 [entrez] PHST- 2018/04/26 06:00 [pubmed] PHST- 2018/04/26 06:01 [medline] PHST- 2018/04/10 00:00 [pmc-release] AID - ott-11-2037 [pii] AID - 10.2147/OTT.S147855 [doi] PST - epublish SO - Onco Targets Ther. 2018 Apr 10;11:2037-2050. doi: 10.2147/OTT.S147855. eCollection 2018.