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

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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 βcatenin are at the center of multiple cancerassociated signaling pathways; therefore, simultaneously targeting STAT3 and βcatenin 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 βcatenin 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 caspase3, cleaved caspase3, poly(ADPribose) polymerase (PARP) and cleaved PARP were determined using western blot analysis. Following siRNA transfection, βcatenin and STAT3 protein levels decreased at 72 h. HepG2 cell growth inhibition and early apoptosis in the βcatenin and STAT3 siRNA cotransfection group were significantly greater than those in the groups transfected with βcatenin or STAT3 siRNA alone. Decreased caspase3 and PARP levels, as well as enhanced cleavage of caspase3 and PARP were observed in the βcatenin and STAT3 cotransfection group. Simultaneous silencing of βcatenin 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 anticancer therapeutic strategies, which target several cancer signaling pathways simultaneously.
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Document Type: Research Article

Affiliations: 1: Department of Gastroenterology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China 2: Department of Gastroenterology, The First Hospital of Harbin, Harbin, Heilongjiang 150000, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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