Activation of Wnt/ β -catenin signalling pathway induces chemoresistance to interferon- α /5-fluorouracil combination therapy for hepatocellular carcinoma

摘要: Type I IFN receptor type 2 (IFNAR2) expression correlates significantly with clinical response to interferon (IFN)-α/5-fluorouracil (5-FU) combination therapy for hepatocellular carcinoma (HCC). However, some IFNAR2-positive patients show no the therapy. This result suggests possibility of other factors, which would be responsible resistance IFN-α/5-FU The aim this study was examine mechanism anti-proliferative effects and search a biological marker chemoresistance such Gene profiling molecular network analysis were used in non-responders responders HCC. Wnt/β-catenin signalling pathway contributed Immunohistochemical showed positive epithelial cell adhesion molecule (Ep-CAM) expression, target signalling, only non-responders. In vitro studies that activation by glycogen synthesis kinase-3 inhibitor (6-bromoindirubin-3′-oxime (BIO)) induced IFN-α/5-FU. BrdU-based proliferation ELISA cycle concurrent addition BIO hepatoma cultures reduced inhibitory latter two on DNA accumulation cells S-phase. results indicate induces suggest Ep-CAM is potentially useful therapy, especially cases.