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Peroxiredoxin 2 is involved in vasculogenic mimicry formation by targeting VEGFR2 activation in colorectal cancer

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Abstract

The mammalian peroxiredoxin 2 (Prdx2) is a member of thiol-dependent antioxidant proteins and plays an important role in the progression of colorectal cancer (CRC). The aim of this study was to confirm the role of Prdx2 in formation of VM and progression of CRC. Immunohistochemistry and CD34/periodic acid Schiff double staining were performed to explore the expression of Prdx2 and VM formation in 70 CRC tissues, and there was a positive correlation between Prdx2 expression and VM formation by the Pearson correlation coefficient (r = 0.282, p < 0.05). Prdx2 was suppressed in poorly differentiated HCT116 cells by Prdx2-siRNA-LV transduction. The expression of Prdx2 at both mRNA and protein levels in HCT116 cells transfected with the Prdx2 siRNA was significantly lower than that of negative control siRNA as confirmed by quantitative real-time PCR and Western blotting analysis, respectively (p < 0.05). The well-established in vitro 3D culture model was chosen to investigate the VM formation of HCT116 cells. The numbers of the tubular structures were significantly fewer in Prdx2 siRNA explants than those of negative control siRNA explants after VEGF induction (p < 0.05). Although VEGFR2 expressions had no change after VEGF induction, we found that VEGFR2 phosphorylation levels were markedly reduced in cells of siPrdx2 over time compared with those of negative control siRNA by Western blotting analysis (p < 0.05, p < 0.01). The effects of Prdx2 siRNA on the invasive capabilities of HCT116 cells with VEGF induction were examined by using Matrigel invasion chamber assay. The invasive capabilities of HCT116 cells were significantly declined in Prdx2 siRNA explants than those of negative control siRNA explants (p < 0.05). The effects of Prdx2 siRNA on pathological tumor growth were examined by using a tumor xenograft model in vivo. After implant of HCT116 cells that transduced with Prdx2 siRNA and negative control siRNA as xenografts into nude mice, the growth of xenograft tumors with Prdx2 siRNA was much slower than that of negative control siRNA, and the volumes of tumor xenografts with Prdx2 siRNA were smaller than those of negative control siRNA after 5 weeks (p < 0.05). Further conclusion showed that Prdx2 regulates VM formation by targeting VEGFR2 activation, which now represents as a therapeutic target for RC.

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Acknowledgments

This study was supported by a Grant from the National Natural Science Foundation of China (No. 81172295).

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All the authors indicate no potential conflict of interest.

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Authors and Affiliations

  1. Department of Gastrointestinal Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Shouru Zhang, Zhongxue Fu, Jinlai Wei, Jinbao Guo, Maoxi Liu & Kunli Du

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  1. Shouru Zhang
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  2. Zhongxue Fu
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  3. Jinlai Wei
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Correspondence to Zhongxue Fu.

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Zhang, S., Fu, Z., Wei, J. et al. Peroxiredoxin 2 is involved in vasculogenic mimicry formation by targeting VEGFR2 activation in colorectal cancer. Med Oncol 32, 414 (2015). https://doi.org/10.1007/s12032-014-0414-9

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  • DOI: https://doi.org/10.1007/s12032-014-0414-9

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