Since a forced activation of Akt, Stat3 and Erk was shown to protect from apoptosis and to induce VEGF expression [40,41], our results suggest that a decreased activation of the IGF-1/IGF-1R-axis due to L.obtusiloba extract treatment contributes to its apoptosis-inducing effects and might be a reason for the reduced expression of VEGF and HIF-1α in HCC cells treated with L.obtusiloba extract [11,12]. This evidence concerns the gene HIF1A and hepatocellular carcinoma.