Recently, two studies by Lu et al. further demonstrated that the growth inhibition and tumor suppressive role of 15-PGDH on hepatocellular carcinoma and intrahepatic cholangiocarcinoma cells were in fact mediated through its enzymatic product 15-keto-PGE2, which in turn activated PPARγ/p21WAF1/Cip1 and PPARγ/Smad2/3/TAP63 signaling cascades respectively [61, 62]. This evidence concerns the gene SMAD2 and hepatocellular carcinoma.