High levels of β-catenin promote IFNγ-induced apoptosis in hepatocellular carcinoma cells.

β-catenin is a multifunctional protein that is involved in cellular structure and the Wnt/β-catenin signaling pathway. Wnt/β-catenin signaling is believed to be an inducer of cell proliferation in different tumors. However, in certain physiological contexts β-catenin also promotes apoptosis. High levels of β-catenin are found in a number of cancer cell types. Recent studies have shown that β-catenin may be correlated with carcinogenesis. Its effects and interaction with interferon (IFN)γ signaling in hepatocellular carcinoma (HCC) cells remains unknown. In the present study, high levels of β-catenin did not induce antiproliferative effects or apoptosis and did not lead to changes in the levels of caspases or activated STATs. However, high levels of β-catenin did cause positive p53 accumulation and Bcl-XL downregulation in HepG2 cells, a HCC cell line. When treated with IFNγ, apoptosis was induced more rapidly compared with cells with low β-catenin levels (P<0.05), whereas caspases 3, 8 and 9 were markedly activated. The caspase inhibitor Z-VAD-FMK and the STAT3 inhibitor blocked this IFNγ-induced apoptosis. Therefore, we report that high levels of β-catenin promote IFNγ-induced apoptosis in HCC in a caspase- and STAT3-dependent manner, and facilitate the activation of executor caspases, possibly via regulation of p53 and Bcl-XL levels. These findings may provide foundations for the development of new IFN-based therapies against liver cancer.