Knockdown of β-catenin by siRNA influences proliferation, apoptosis and invasion of the colon cancer cell line SW480.

The aim of the present study was to explore the effect of knocking down the expression of β-catenin by small interference (si)RNA on the activity of the Wnt/β-catenin signaling pathway, and the proliferation, apoptosis and invasion abilities of the human colon cancer cell line SW480. For that purpose, double-stranded siRNA targeting β-catenin (β-catenin-siRNA) was synthesized and transfected into SW480 cells. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were used to detect the messenger (m)RNA and protein levels of β-catenin in SW480 cells. To detect cell proliferation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed, while cell apoptosis and caspase-3 activity were detected by flow cytometry and caspase-3 activity assay, respectively. Matrigel invasion assay was performed to detect the influence of siRNA-mediated gene silencing on the invasion and metastasis of SW480 cells in vitro. The results of RT-PCR and western blot analysis demonstrated that, compared with the blank control, negative control and liposome groups, β-catenin-siRNA transfected SW480 cells had significantly decreased mRNA and protein levels of β-catenin. In addition, following β-catenin-siRNA transfection, the proliferation of SW480 cells was significantly lower than that of the blank control, negative control and liposome groups, while the apoptosis rate increased in β-catenin-siRNA transfected cells, compared with the aforementioned groups. Invasion assay showed that, following β-catenin-siRNA transfection, the number of SW480 cells infiltrating through the Matrigel membrane was significantly lower than that of the blank control, negative control and liposome groups. Following β-catenin-siRNA transfection, the caspase-3 activity in SW480 cells was lower than that in the blank control, negative control and liposome groups. These results indicate that siRNA-mediated silencing of β-catenin could inhibit the proliferation and invasion of SW480 cells and induce apoptosis, thus providing novel potential strategies for the clinical treatment of colon cancer, and may serve as a novel target for cancer therapy.

[1]  Chao Zhao,et al.  Wnt/β-catenin signaling induces the transcription of cystathionine-γ-lyase, a stimulator of tumor in colon cancer. , 2014, Cellular signalling.

[2]  R. Gosens,et al.  β-catenin as a regulator and therapeutic target for asthmatic airway remodeling , 2014, Expert opinion on therapeutic targets.

[3]  Michael Kahn,et al.  Wnt/Catenin Signaling in Adult Stem Cell Physiology and Disease , 2014, Stem Cell Reviews and Reports.

[4]  Í. Lopes-Cendes,et al.  The new world of RNAs , 2013, Genetics and molecular biology.

[5]  J. Lammerding,et al.  Nuclear mechanics in cancer. , 2014, Advances in experimental medicine and biology.

[6]  Christof Fellmann,et al.  Stable RNA interference rules for silencing , 2013, Nature Cell Biology.

[7]  K. Vlahovicek,et al.  A Retrotransposon-Driven Dicer Isoform Directs Endogenous Small Interfering RNA Production in Mouse Oocytes , 2013, Cell.

[8]  D. Lu,et al.  Targeting the Wnt/beta-catenin pathway in multiple myeloma. , 2013, Anticancer research.

[9]  B. Liagre,et al.  Novel methylsulfonyl chalcones as potential antiproliferative drugs for human prostate cancer: involvement of the intrinsic pathway of apoptosis. , 2013, International journal of oncology.

[10]  C. Chiaro,et al.  p300 Influences Butyrate-Mediated WNT Hyperactivation In Colorectal Cancer Cells , 2013, Journal of Cancer.

[11]  S. Krauss,et al.  Wnt/beta-Catenin Signaling and Small Molecule Inhibitors , 2012, Current pharmaceutical design.

[12]  Hans Clevers,et al.  Wnt/β-Catenin Signaling and Disease , 2012, Cell.

[13]  Chin Wee Tan,et al.  Wnt Signalling Pathway Parameters for Mammalian Cells , 2012, PloS one.

[14]  F. Tsai,et al.  β-catenin plays a key role in metastasis of human hepatocellular carcinoma. , 2011, Oncology reports.

[15]  H. Yao,et al.  Targeting the Wnt/β-catenin signaling pathway in human cancers , 2011, Expert opinion on therapeutic targets.

[16]  S. Paul,et al.  Wnt signaling and cancer development: therapeutic implication. , 2008, Neoplasma.

[17]  Riccardo Fodde,et al.  Wnt/β-catenin signaling in cancer stemness and malignant behavior , 2007 .

[18]  R. Fodde,et al.  Wnt/beta-catenin signaling in cancer stemness and malignant behavior. , 2007, Current opinion in cell biology.

[19]  J. Behrens,et al.  Control of β‐Catenin Signaling in Tumor Development , 2000 .

[20]  J. Behrens,et al.  Control of beta-catenin signaling in tumor development. , 2000, Annals of the New York Academy of Sciences.