WITHDRAWN: Modulation on gallbladder carcinoma by TGF-β1 via IGFBP-2

Ahead of Print article withdrawn by publisher. Gallbladder carcinoma (GC) occupies more than 90% of all cancers in biliary tract with an increasing incidence. Most patients with GC are already at terminal stage at the time of primary diagnosis, causing unfavorable prognosis and high mortality. Transformation growth factor-beta (TGF-β) is up-regulated in GC. However, the mechanism by how TGF-β is involved in GC remains unclear. The aim of this study was to investigate the effect and mechanism of TGF-β in GC using GC cell line NOZ cells.In vitro cultured NOZ cell was randomly assigned into control, si-NC and TGF-β1 siRNA groups and were transfected with siRNA negative control (NC) or TGF-β1 siRNA followed by analysis of TGF-β1 expression by Real-time PCR, cell proliferation by MTT assay, cell apoptosis and cell invasion, as well as expression of proteins in epithelial-mesenchymal transition (EMT), p38, Smad2/3 and Smad4 phosphorylation by Western blot, Insulin-like growth factor-binding protein-2 (IGFBP-2) level by ELISA. After transfecting TGF-β1 siRNA into NOZ cells, TGF-β1 expression was suppressed and cell proliferation and invasion were inhibited, together with enhanced Caspase-3 activity. Meanwhile, E-cadherin expression was increased, with decreased Vimentin, IGFBP-2, p38, Smad2/3 and Smad4 phosphorylation (P< 0.05 comparing to control group). In conclusion, inhibition of TGF-β1 expression facilitates GC cell apoptosis, inhibits GC cell proliferation, invasion and EMT occurrence.