“…The hepatocellular carcinoma model determined that cell proliferation was inhibited by an increase in p21 WAF1/Cip1 (cyclin-dependent kinase inhibitor 1) expression, leading to downstream association with cyclin-dependent kinase (CDK2), CDK4, and proliferating cell nuclear antigen (12). In the cholangiocarcinoma model, inhibition of proliferation is acquired through PPAR␥-, (SMAD2/3)-, and Tap63 (tumor protein)-mediated signaling actions (13). This study also linked 15-ketoPGE 2 generation with the induction of SMAD 2/3 dissociation from PPAR␥, thus promoting SMAD 2/3 complex formation with transforming growth factor B receptor 1 and SMAD anchor receptor for acti- vation.…”