Tumor Biology

, Volume 36, Issue 8, pp 6285–6293 | Cite as

A Huaier polysaccharide reduced metastasis of human hepatocellular carcinoma SMMC-7721 cells via modulating AUF-1 signaling pathway

  • Cong Li
  • Xia Wu
  • Honghai Zhang
  • Gengxia Yang
  • Meijun Hao
  • Shoupeng Sheng
  • Yu Sun
  • Jiang Long
  • Caixia Hu
  • Xicai Sun
  • Li Li
  • Jiasheng Zheng
Research Article


TP-1 is a polysaccharide from one famous fungus Huaier. Treatment with TP-1 significantly inhibited the cell growth, adhesion, migration, and motility of SMMC-7721 cells in a dose-dependent manner. Real-time quantitative RT-PCR revealed a dose-dependent decrease in RNA-binding factor 1 (AUF-1) and astrocyte elevated gene-1 (AEG-1) messenger RNA (mRNA) levels in TP-1-treated SMMC-7721 cells, which is consistent with their protein expression detected by Western blotting. On the contrary, microRNA-122 (miR-122) expression increased in SMMC-7721 cells following TP-1 treatment. Moreover, TP-1 treatment at three doses apparently increased epithelial marker E-cadherin protein expression but decreased the mesenchymal marker N-cadherin protein level. In addition, the hematoxylin-eosin (H & E) staining showed that the TP-1 significantly inhibited the lung metastasis of liver cancer in mice orthotopic implanted with SMMC-7721 tumor tissue. Taken together, these findings proved the inhibitory effect of TP-1 on the growth and metastasis of SMMC-7721 cells, and TP-1 might be offered for future application as a powerful chemopreventive agent against hepatocellular carcinoma (HCC) metastasis.


Huaier polysaccharide Metastasis Hepatocellular carcinoma RNA-binding factor 1 (AUF-1) Astrocyte elevated gene-1 (AEG-1) Epithelial-mesenchymal transition (EMT) 



This research is funded by the National Natural Science Foundation of China (grant no. 81472328); Liver Disease AIDS Foundation of You An Hospital, Capital Medical University (BJYAH-2011-034); National Science and Technology Support Project (2012BAI15B08); and Key Project of National Communicable Disease (2012ZX10002015-002).

Conflicts of interest

The authors declare that they have no conflicts of interest concerning this article.


  1. 1.
    Zhang CL, Zeng T, Zhao XL, Yu LH, Zhu ZP, Xie KQ. Protective effects of garlic oil on hepatocarcinoma induced by N-nitrosodiethylamine in rats. Int J Biol Sci. 2012;8:363–74.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Sporn MB. The war on cancer. Lancet. 1996;347:1377–81.CrossRefPubMedGoogle Scholar
  3. 3.
    Fidler IJ. Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture. Cancer Res. 1990;50:6130–8.PubMedGoogle Scholar
  4. 4.
    Arvelo F, Cotte C. Metalloproteinases in tumor progression. Review. Invest Clin. 2006;47:185–205.PubMedGoogle Scholar
  5. 5.
    Yang Y, Kang P, Gao J, Xu C, Wang S, Jin H, et al. AU-binding factor 1 expression was correlated with metadherin expression and progression of hepatocellular carcinoma. Tumour Biol. 2014;35:2747–51.CrossRefPubMedGoogle Scholar
  6. 6.
    Zheng J, Li C, Wu X, Yang Y, Hao M, Sheng S, et al. Astrocyte elevated gene-1 is a novel biomarker of epithelial–mesenchymal transition and progression of hepatocellular carcinoma in two China regions. Tumour Biol. 2014;35:2265–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Nakao K, Miyaaki H, Ichikawa T. Antitumor function of microRNA-122 against hepatocellular carcinoma. J Gastroenterol. 2014;49:589–93.CrossRefPubMedGoogle Scholar
  8. 8.
    Zheng J, Li C, Wu X, Liu M, Sun X, Yang Y, et al. Huaier polysaccharides suppresses hepatocarcinoma MHCC97-H cell metastasis via inactivation of EMT and AEG-1 pathway. Int J Biol Macromol. 2014;64:106–10.CrossRefPubMedGoogle Scholar
  9. 9.
    Staub AM. Removal of protein—Sevag method. Methods Carbohydr Chem. 1965;5:5–6.Google Scholar
  10. 10.
    Tian J, Che H, Ha D, Wei Y, Zheng S. Characterization and anti-allergic effect of a polysaccharide from the flower buds of Lonicera japonica. Carbohydr Polym. 2012;90:1642–7.CrossRefPubMedGoogle Scholar
  11. 11.
    Dubois M, Gilles KA, Hamilton JK, Rebers PA, Smith F. Colorimetric method for determination of sugars and related substances. Anal Chem. 1956;28:350–6.CrossRefGoogle Scholar
  12. 12.
    Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein binding. Anal Biochem. 1976;72:248–54.CrossRefPubMedGoogle Scholar
  13. 13.
    Blumenkrantz N, Asboe-Hansen G. New method for quantitative determination of uronic acids. Anal Biochem. 1973;54:484–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55–63.CrossRefPubMedGoogle Scholar
  15. 15.
    Saiki I, Iida J, Murata J, Ogawa R, Nishi N, Sugimura K, et al. Inhibition of the metastasis of murine malignant melanoma by synthetic polymeric peptides containing core sequences of cell-adhesive molecules. Cancer Res. 1989;49:3815–22.PubMedGoogle Scholar
  16. 16.
    Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 2001;25:402–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Man K, Ng KT, Xu A, Cheng Q, Lo CM, Xiao JW, et al. Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of Rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signaling. Clin Cancer Res. 2010;16:967–77.CrossRefPubMedGoogle Scholar
  18. 18.
    Sun FX, Tang ZY, Lui KD, Ye SL, Xue Q, Gao DM, et al. Establishment of a metastatic model of human hepatocellular carcinoma in nude mice via orthotopic implantation of histologically intact tissues. Int J Cancer. 1996;66:239–43.CrossRefPubMedGoogle Scholar
  19. 19.
    Micalizzi DS, Farabaugh SM, Ford HL. Epithelial-mesenchymal transition in cancer: parallels between normal development and tumor progression. J Mammary Gland Biol Neoplasia. 2010;15:117–34.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Cai JP, Wu YJ, Li C, Feng MY, Shi QT, Li R, et al. Panax ginseng polysaccharide suppresses metastasis via modulating Twist expression in gastric cancer. Int J Biol Macromol. 2013;57:22–5.CrossRefPubMedGoogle Scholar
  21. 21.
    Entschladen F, Drell 4th TL, Lang K, Joseph J, Zaenker KS. Tumour-cell migration, invasion, and metastasis: navigation by neurotransmitters. Lancet Oncol. 2004;5:254–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Ng KT, Guo DY, Cheng Q, Geng W, Ling CC, Li CX, et al. A garlic derivative, S-allylcysteine (SAC), suppresses proliferation and metastasis of hepatocellular carcinoma. PLoS One. 2012;7:e31655.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Feng YX, Wang T, Deng YZ, Yang P, Li JJ, Guan DX, et al. Sorafenib suppresses postsurgical recurrence and metastasis of hepatocellular carcinoma in an orthotopic mouse model. Hepatology. 2011;53:483–92.CrossRefPubMedGoogle Scholar
  24. 24.
    Tang ZY, Ye SL, Liu YK, Qin LX, Sun HC, Ye QH, et al. A decade’s studies on metastasis of hepatocellular carcinoma. J Cancer Res Clin Oncol. 2004;130:187–96.CrossRefPubMedGoogle Scholar
  25. 25.
    Zheng J, Li C, Wu X, Liu M, Sun X, Yang Y, et al. Astrocyte elevated gene-1 (AEG-1) shRNA sensitizes Huaier polysaccharide (HP)-induced anti-metastatic potency via inactivating downstream P13K/Akt pathway as well as augmenting cell-mediated immune response. Tumour Biol. 2014;35:4219–24.CrossRefPubMedGoogle Scholar
  26. 26.
    Gu Y, Zhu CF, Dai YL, Zhong Q, Sun B. Inhibitory effects of genistein on metastasis of human hepatocellular carcinoma. World J Gastroenterol. 2009;15:4952–7.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Rouhi P, Lee SL, Cao Z, Hedlund EM, Jensen LD, Cao Y. Pathological angiogenesis facilitates tumor cell dissemination and metastasis. Cell Cycle. 2010;9:913–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Köberle V, Kronenberger B, Pleli T, Trojan J, Imelmann E, Peveling-Oberhag J, et al. Serum microRNA-1 and microRNA-122 are prognostic markers in patients with hepatocellular carcinoma. Eur J Cancer. 2013;49:3442–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Xu J, Zhu X, Wu L, Yang R, Yang Z, Wang Q, et al. MicroRNA-122 suppresses cell proliferation and induces cell apoptosis in hepatocellular carcinoma by directly targeting Wnt/β-catenin pathway. Liver Int. 2012;32:752–60.CrossRefPubMedGoogle Scholar
  30. 30.
    Tsai WC, Hsu PW, Lai TC, Chau GY, Lin CW, Chen CM, et al. MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology. 2009;49:1571–82.CrossRefPubMedGoogle Scholar
  31. 31.
    Wang L, Alcon A, Yuan H, Ho J, Li QJ, Martins-Green M. Cellular and molecular mechanisms of pomegranate juice-induced anti-metastatic effect on prostate cancer cells. Integr Biol (Camb). 2011;3:742–54.CrossRefGoogle Scholar
  32. 32.
    Yoon JH, Choi YJ, Cha SW, Lee SG. Anti-metastatic effects of ginsenoside Rd via inactivation of MAPK signaling and induction of focal adhesion formation. Phytomedicine. 2012;19:284–92.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Cong Li
    • 1
  • Xia Wu
    • 2
  • Honghai Zhang
    • 1
  • Gengxia Yang
    • 1
  • Meijun Hao
    • 1
  • Shoupeng Sheng
    • 1
  • Yu Sun
    • 1
  • Jiang Long
    • 1
  • Caixia Hu
    • 1
  • Xicai Sun
    • 3
  • Li Li
    • 4
  • Jiasheng Zheng
    • 1
  1. 1.Intervention Therapy Center of Liver Diseases, Beijing You An HospitalCapital Medical UniversityBeijingChina
  2. 2.Department of Infectious Diseasethe Second Affiliated Hospital of Harbin Medical UniversityHarbinChina
  3. 3.School of Medicine, Tsinghua Center for Life SciencesTsinghua UniversityBeijingChina
  4. 4.Institute of Liver Diseases, Beijing You An HospitalCapital Medical UniversityBeijingChina

Personalised recommendations