The
tumorigenesis and maintenance of a
cancer cells is dependent upon the collaboration of multiple signaling pathways.
Signal transducer and activator of transcription 3 (STAT3) and β-
catenin are at the center of multiple
cancer-associated signaling pathways; therefore, simultaneously targeting STAT3 and β-
catenin may be a potential
cancer treatment, leading to induced lethality of
cancer cells. In the present study, HepG2
liver cancer cells were transfected with
small interfering RNA (
siRNA) against β-
catenin and STAT3 alone or in combination. The cell growth was assessed using an MTT assay and the levels of cell apoptosis were detected using flow cytometry.
Protein levels of
caspase-3, cleaved
caspase-3,
poly(ADP-ribose) polymerase (PARP) and cleaved PARP were determined using western blot analysis. Following
siRNA transfection, β-
catenin and
STAT3 protein levels decreased at 72 h. HepG2 cell growth inhibition and early apoptosis in the β-
catenin and STAT3
siRNA co-transfection group were significantly greater than those in the groups transfected with β-
catenin or STAT3
siRNA alone. Decreased
caspase-3 and PARP levels, as well as enhanced cleavage of
caspase-3 and PARP were observed in the β-
catenin and STAT3 co-transfection group. Simultaneous silencing of β-
catenin and STAT3 using siRNAs resulted in an enhanced loss of cell viability and induction of apoptosis in HepG2
liver cancer cells, suggesting that these genes are promising targets for the further preclinical and clinical development of anti-
cancer therapeutic strategies, which target several
cancer signaling pathways simultaneously.