Elsevier

Neoplasia

Volume 9, Issue 11, November 2007, Pages 951-959
Neoplasia

siRNA-Mediated β-Catenin Knockdown in Human Hepatoma Cells Results in Decreased Growth and Survival*

https://doi.org/10.1593/neo.07469Get rights and content
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open access

Abstract

β-Catenin, the chief oncogenic component of the canonical Wnt pathway, is known to be involved in a variety of cancers, including hepatocellular carcinoma (HCC). Although the mechanism of β-catenin activation in HCC is multifactorial, it is indisputably implicated at various stages of hepatocarcinogenesis, making it an attractive therapeutic target. Here we investigate the effect of small interfering RNA-mediated β-catenin knockdown on the growth and survival of human hepatoma cell lines with (HepG2) and without (Hep3B) β-catenin mutations. Transfection of HepG2 and Hep3B cells with human β-catenin (CTNNBl) small interfering RNA resulted in a significant β-catenin decrease, as confirmed by Western blot analyses and immunofluorescence, also leading to decreased expression of known target genes such as cyclin D1 and glutamine synthetase. The decrease in β-catenin activity was confirmed by TOPflash reporter luciferase assay. The functional impact of diminished β-catenin was exhibited as temporal decrease in tumor cell viability by the MTT assay. A concomitant decrease in tumor cell proliferation was also evident with [3H]thymidine incorporation and verified with soft agar assays. Thus, β-catenin is essential for the survival and growth of hepatoma cells independent of mutations in the β-catenin gene and provide a proof of principle for the significance of the therapeutic inhibition of β-catenin in HCC.

Keywords

Liver cancer
Wnt/β-catenin
development
treatment
regeneration

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*

1This report was funded, in part, by the American Cancer Society (grant RSG-03-141-01-CNE to S.P.S.M.) and the National Institutes of Health (grants 1RO1DK62277 and 1R01CA124414 to S.P.S.M.) Rango's Fund for Enhancement of Pathology Research.