Table 1.

Molecular therapies targeting Wnt/β-catenin pathway in hepatocellular carcinoma

Compound	Target in vitro	Target in vivo
Sorafenib[4]	Decrease of TCF/LEF, β-catenin protein levels and Wnt-target genes mRNA levels[11]	Decrease tumor volume and increase survival of treated animals in HepG2 xenografts in nude mice[11]
sFZD7[66]	Block interaction between. FZD and Dvl. Decrease viability of HepG2, Hep40 and Huh7 cell lines. Reduced expression of c-Myc, Cyclin D1 and Survivin. The effect was potentiated in combination with Doxorubicin[66]	Inhibitory effect in Huh7 xenografts[66]
RHPDs[67]	Decrease viability of human HCC cell lines (Huh7 and HepG2) through degradation of β-catenin and activation of PKCδ in a TP53-independent manner[67]	Intratumor injection in SV40-TAg transgenic mouse model inhibited HCC progression[67]
BrMC[42]	Inhibition of CD133+ LCSCs proliferation, EMT and invasion in MHCC97 cell line, and decreased expression of beta-catenin in this LCSCs[42]	Inhibition of LCSCs proliferation in Balb/c-nu mice xenografts model[42]
SL1122-37[71] (Sorafenib derivative)	Inhibitory effect on the proliferation of HCC PLC/PRF/5 cells and the formation of angiogenesis of HUVECs[71]
PMED-1[18]	Blocks β-catenin and CBP interaction. Suppression of down-stream effects in β-catenin signaling in HCC cell lines[18]	Decrease of Wnt signaling in transgenic zebrafish[18]
XAV939[61]	Inhibit Tankyrase 1 and 2 inducing degradation of β-catenin by stabilization of Axin. Antitumor activity against neuroblastoma[72], colon[73], breast[74] and lung[75] cancers, and HCC Decreased nuclear β-catenin levels, cell proliferation and colony formation in HepG2 and Huh7[76].	Inhibited growth of HepG2 xenograft model of HCC[76]. Reduce tumor growth in a conditional APC mutant mouse model of colon cancer[73]. Repressed lung cancer formation in murine xenograft and transgenic syngeneic lung cancer models[75]
CGP049090	Block TCF/LEF and β-catenin interaction. Decrease expression of c-myc, Cyclin D1 and Survivin in AML[56], CCL[57], MM[55] and HCC[58,59] cells. Induced apoptosis and cell cycle arrest at the G1/S phase.	Inhibitory effect in murine xenograft model of human MM[55], HepG2 xenograft model of HCC[58], JVM-3 subcutaneous xenograft model of CCL[57]
PKF115-854
PKF118-310[54]
FH535[69]	Inhibition of the activation of β-catenin-regulated genes in the HCC cell lines Huh7, Hep3B and PLC and LCSC. Arrests the cell cycle from G1 to S-phase[69]
FH535 and Sorafenib combination[12]	Synergistic inhibition of LCSC and Huh7 cell lines proliferation. Dose dependent inhibition of Cyclin D1, Survivin and Bcl2 expression[12]

LEF/TCF: Lymphoid enhancer factor/T-cell factor; HCC: Hepatocellular carcinoma; LCSCs: Liver cancer stem cells.