Figure 8. Suppression of PIK3CA and Yap activity via specific inhibitors is highly detrimental for the growth of human HLF hepatocellular carcinoma (HCC) cell line and the human EGI1 cholangiocarcinoma (CCA) cell line.

(A) Treatment with the PIK3CA inhibitor, PIK75 (1 μM), or the Yap/TEAD disruptor, Verteporfin (Verte; 2 μM) decreased proliferation (left panel) and induced apoptosis (center panel) in the HLF HCC cell line when compared with control (untreated) and DMSO (solvent) treated cells. Of note, combined administration of PIK75 and Verteporfin further decreased the proliferation rate of HLF cells without further augmenting apoptosis. The effects of PIK75 and Verteporfin treatment on PIK3CA targets (phosphorylated-NDRG1 and phosphorylated/inactivated 4EBP1) as wells as on Yap and its effector, CTGF, in HLF cells were assessed by Western blot analysis (right panel). (B) A similar growth restraint patterns as those described in (A) was also detected when the EGI1 CCA cell line was subjected to the administration of the two inhibitors, either alone or in combination. Once again, the additive effects of the two drugs affected only the proliferation rate but not the apoptosis activity in EGI1 cells. The effects of PIK75 and Verteporfin treatment on PIK3CA targets (phosphorylated-NDRG1 and phosphorylated/inactivated 4EBP1) as wells as on Yap and its effector, CTGF, in EGI1 cells were assessed by Western blot analysis (right panel). Each bar represent mean ± SD of three independent experiments conducted in triplicate. Tukey-Kramer's test: P at least < 0.001 a, versus control (untreated cells); b, versus DMSO (solvent); c, versus PIK75; d, versus Verteporfin. Abbreviation: Verte, Verteporfin.