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A polysaccharide from mushroom Huaier retards human hepatocellular carcinoma growth, angiogenesis, and metastasis in nude mice

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Tumor Biology

Abstract

Mushroom Huaier has become a focus of interest in the treatment of hepatocellular carcinoma (HCC). Presently, we isolated and purified one polysaccharide from this mushroom. This study aimed to investigate the effects of SP1 on tumor growth and metastasis in a HCC xenograft model and explore its possible mechanism of action. Our results showed that SP1 not only significantly inhibited the proliferation of SMMC-7721 cells in vitro at the concentration ranging from 0 to 800 μg/ml but also suppressed the HCC tumor growth and metastatic nodules to the lung in SMMC-7721-bearing mice by oral administration at three doses of 30, 60, and 120 mg/kg. Concomitantly, immunohistochemistry analysis of tumor tissues identified that SP1 administration at three doses significantly inhibited the in vivo cancer cell proliferation and microvessel density (MVD) formation, evidenced by a low proliferating cell nuclear antigen (PCNA) and CD34 expression, but increased the percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells. Keeping in line with this observation, SP1 treatment decreased serum matrix metalloproteinase (MMP) 2 and vascular endothelial growth factor (VEGF) levels, downregulated the protein expression of hypoxia-inducible factor (HIF)-1alpha, VEGF, MMP2, bcl-2, N-cadherin, signal transducer and activator of transcription 3 (STAT3), and metadherin (MTDH), and upregulated bax and NE-cadherin protein expression in tumor tissues. Taken together, our data suggest that SP1 appears to be a promising chemopreventive agent for the tumorigenesis and metastasis in patients with HCC, especially at advanced stages.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81201779 and No. 81101691).

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Authors and Affiliations

  1. Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Yanmei Zou, Hua Xiong, Huihua Xiong & Xianglin Yuan

  2. Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China

    Tao Lu & Feng Zhu

  3. Division of Breast and Thyroid Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Zhiyong Luo

  4. Ludwig Institute for Cancer Research Ltd., Nuffield, Department of Clinical Medicine, University of Oxford, Oxford, OX3 7DQ, UK

    Yihua Wang

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  1. Yanmei Zou
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  2. Hua Xiong
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  3. Huihua Xiong
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  4. Tao Lu
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Correspondence to Hua Xiong.

Additional information

Yanmei Zou and Xiaomin Qin contributed equally to this work.

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Zou, Y., Xiong, H., Xiong, H. et al. A polysaccharide from mushroom Huaier retards human hepatocellular carcinoma growth, angiogenesis, and metastasis in nude mice. Tumor Biol. 36, 2929–2936 (2015). https://doi.org/10.1007/s13277-014-2923-8

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  • DOI: https://doi.org/10.1007/s13277-014-2923-8

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