Simultaneous silencing of β-catenin and signal transducer and activator of transcription 3 synergistically induces apoptosis and inhibits cell proliferation in HepG2 liver cancer cells.

Abstract

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.

• Authors: Xin-Hong Wang, Ming-Na Liu, Ping Huang, Jun Xu, Ai-Yun Liu, Jing Chen, Cheng-Qian Lv, Rui-Ling Xu
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 12 Issue 2 Pg. 2263-8 (Aug 2015) ISSN: 1791-3004 [Electronic] Greece
• PMID: 25845340 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CTNNB1 protein, human
• RNA, Small Interfering
• STAT3 Transcription Factor
• STAT3 protein, human
• beta Catenin
• Poly(ADP-ribose) Polymerases
• Caspase 3

Topics

• Apoptosis (genetics)
• Caspase 3 (genetics, metabolism)
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Gene Silencing
• Hep G2 Cells
• Humans
• Poly(ADP-ribose) Polymerases (genetics, metabolism)
• Proteolysis
• RNA, Small Interfering (genetics, metabolism)
• STAT3 Transcription Factor (antagonists & inhibitors, genetics, metabolism)
• Signal Transduction
• beta Catenin (antagonists & inhibitors, genetics, metabolism)