Therapeutic Effects And Mechanisms Of Reic/Dkk3 Modified Human Umbilical MSCs To Bladder Cancer

Aim: Urinary bladder cancer is the most commonly diagnosed malignancy of urinary tract.Wnt/β-catenin signaling pathway is involved in bladder carcinogenesis,progression and invasion.Reic/Dkk3 has negative function in regulating Wnt signaling which also shows cancer inhibiting property in several studies.However,the inhibition of Reic/Dkk3 to cancer lacks tumor tropism which impedes the clinic implication of Reic/Dkk3.Mesenchymal stem cells attract great attention because they target tumor microenvironment.Taking advantage of this special ability of MSCs,we intended to construct MSCs which stable express Reic/Dkk3 and verify its inhibiting effects on T24 cell.Methods:(1).Isolate and characterize human umbilical cord mesenchymal stem cells(2).Construct lenti-virus vector over expressing Reic/Dkk3 and tranfected to HUC-MSCs.Then,verify HUC-MSCs’ feature change.(3).Co-culture supernatant of HUC-MSCs-Dkk3 with T24 cells.Test cell proliferation,migration,invasion change of T24(4)Explain the mechanisms of β-catenin mediated bladder cancer metastasis.Results: 1.HUC-MSCs were successfully isolated and characterize as the given criterion.2.Dkk3 modification only increased Dkk3 secreting of HUC-MSCs without altering other properties..3.Supernatants of HUC-MSCs-Dkk3 inhibit T24 cells’ malignacy in vitro.4.β-catenin regulates tumor invasion through mediation of MMP9 production.Conclusion: HUC-MSCs over-expressing Dkk3 inhibit T24 cells’ malignacy efficiently,β-catenin mediated Wnt activation induces MMP9 production which leads to tumor invasion.