Mechanistically, calcitriol suppressed EMT through different signaling pathways: (1) calcitriol suppressed Smad2/3 phosphorylation through reinforcing physical interaction between vitamin D receptor (VDR) and Smad3 in TGF-β1-stimulated RCC cells; (2) calcitriol inhibited STAT3 activation in LPS-stimulated RCC cells; (3) calcitriol inhibited β-catenin/TCF-4 activation through promoting integration of VDR with β-catenin in TGF-β1-unstimulated RCC cells.
We also analyzed the relationship between TCF-4 gene splicing isoforms, proliferation (proliferating cell nuclear antigen labeling index), and apoptosis [antiapoptotic factors (Bcl-2 and Bcl-x(L)), proapoptotic factors (Bak and Bax), and caspase-3] in RCC samples.