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Synergistic effect of indomethacin and NGX6 on proliferation and invasion by human colorectal cancer cells through modulation of the Wnt/β-catenin signaling pathway

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Abstract

This study was designed to investigate whether indomethacin and NGX6 synergistically inhibit the growth and invasiveness of human colon cancer cells (HT-29 and SW620) and to elucidate the molecular mechanism of their action. Cell proliferation was assessed by MTT assay. Cell apoptosis was assessed by acridine orange/ethidium bromide staining (AO–EB) and annexin-V-FITC/PI assay. Invasive behaviors of colorectal cancer cells were examined by cell adhesion, migration, and invasion assays. Gap junctional intercellular communication (GJIC) was assessed by the scrape-loading/dye transfer technique. The subcellular localization and expression of β-catenin protein was examined by immunofluorescence staining and western blot analysis, respectively. Indomethacin and NGX6 had a synergistic effect on inhibiting proliferation and invasiveness of colon cancer HT-29 and SW620 cells, restoring GJIC of HT-29 and SW620, and suppressing translocation of β-catenin from the nucleus and cytoplasm to the plasma membrane. However, they did not have synergistic effects on enhancing apoptosis and suppressing extracellular matrix adhesion of HT-29 and SW620 cells. Indomethacin and NGX6 inhibit the proliferation and invasiveness of HT-29 and SW620 colon cancer cells by attenuating the WNT/ß-catenin signaling pathway.

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Acknowledgments

We gratefully acknowledge for the financial assistance granted by the State Key Science Research Program of China (2006CB910503); the National Natural Science Foundation of China (30770972, 30770825); China Postdoctoral Science Foundation (20060400265); the Hunan Province Natural Sciences Foundations of China (06JJ20068, 07JJ3057); Research Fund for the Doctoral Program of Higher Education of China (20070533031)

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Authors and Affiliations

  1. Department of Digestion Medicine, The Third Affiliated Hospital of Xiang Ya School of Medicine, Central South University, Changsha, 410078, Hunan, People’s Republic of China

    Qin Guo, Minghua Wu, Ping Lian, Mantian Liao, Zhiming Xiao, Xiaoyan Wang & Shourong Shen

  2. Cancer Research Institute, Central South University, Changsha, 410078, Hunan, People’s Republic of China

    Minghua Wu

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  1. Qin Guo
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  2. Minghua Wu
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  3. Ping Lian
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  4. Mantian Liao
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  5. Zhiming Xiao
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  6. Xiaoyan Wang
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  7. Shourong Shen
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Correspondence to Shourong Shen.

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Guo, Q., Wu, M., Lian, P. et al. Synergistic effect of indomethacin and NGX6 on proliferation and invasion by human colorectal cancer cells through modulation of the Wnt/β-catenin signaling pathway. Mol Cell Biochem 330, 71–81 (2009). https://doi.org/10.1007/s11010-009-0102-9

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  • DOI: https://doi.org/10.1007/s11010-009-0102-9

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