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Glycyrrhiza polysaccharide induces apoptosis and inhibits proliferation of human hepatocellular carcinoma cells by blocking PI3K/AKT signal pathway

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Tumor Biology

Abstract

To study the antitumor effect of glycyrrhiza polysaccharide (GPS) on human hepatocellular carcinoma cells and its mechanism, GPS was extracted and identified with phenol–sulfuric acid assay, Limulus amebocytes lysate assay, gel permeation chromatography, and infrared spectroscopy analysis. To study its antitumor function, 4–5-week-old imprinting control region mice were subcutaneously implanted with H22 cells and intragastrically subjected to 1 ml GPS (25, 50, and 75 mg/kg/day), 150 mg/kg cyclophosphamide in a dose of 150 mg/kg, or equal volume of phosphate buffered saline as control. Tumor weights were detected 10 days later. Apoptosis of intraperitoneally cultured and GPS-treated H22 cells was identified by flow cytometry and 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolyl-carbocyanine iodide. In vitro, the function of GPS on cell proliferation was applied on BEL7402 cells and confirmed by 4,6-diamidino-z-phenylindole staining. Assessment of the effect of GPS on P53 gene was analyzed by real-time PCR and Western blot, and the effects of GPS on phosphatidylinositol-3 kinase (PI3K), AKT, p-PI3K, and p-AKT were analyzed by Western blot. We extracted the GPS, and it dose-dependently inhibited the tumorigenicity of hepatocellular carcinoma cells in nude mice. GPS treatment resulted in a significant (P < 0.05) dose-dependent increase in the number of apoptotic cells in vivo and a significant (P < 0.05) dose-dependent decrease in hepatocellular carcinoma cell proliferation in vitro. GPS modified multiple key enzymes (p-PI3K, p-AKT, and P53) in P53/PI3K/AKT signaling pathways on DNA or protein levels. Taken together, we extracted the GPS successfully and our findings suggest that GPS functions as a tumor suppressor through influencing the P53/PI3K/AKT pathway in the carcinogenesis of hepatocellular carcinoma and may have therapeutic implications for the clinical management of hepatocellular carcinoma patients.

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Acknowledgments

This study was supported by the grants from Zhejiang Natural Science Foundation (Y2100248), Foundation of Department of Science and Technology of Zhejiang Province (2009C33155), Foundation of Zhejiang Health Department (2009A218), Taizhou Science and Technology Bureau (102KY15), and Zhejiang Province Chinese medicine study foundation (2011ZA113).

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Authors and Affiliations

  1. Medical School of Taizhou University, Taizhou, Zhejiang, 318000, China

    Jiayu Chen & Jie Chen

  2. Department of Oncology, Taizhou Municipal Hospital, Taizhou, Zhjiang, 318000, China

    Xiaoyan Jin

  3. Department of Clinical Laboratory, Taizhou Municipal Hospital, Taizhou, Zhjiang, 318000, China

    Chibo Liu

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  1. Jiayu Chen
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  2. Xiaoyan Jin
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  3. Jie Chen
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  4. Chibo Liu
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Correspondence to Jiayu Chen or Chibo Liu.

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Chen, J., Jin, X., Chen, J. et al. Glycyrrhiza polysaccharide induces apoptosis and inhibits proliferation of human hepatocellular carcinoma cells by blocking PI3K/AKT signal pathway. Tumor Biol. 34, 1381–1389 (2013). https://doi.org/10.1007/s13277-013-0746-7

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  • DOI: https://doi.org/10.1007/s13277-013-0746-7

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