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.

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