Tumor Biology

, Volume 36, Issue 3, pp 1739–1745 | Cite as

A Huaier polysaccharide inhibits hepatocellular carcinoma growth and metastasis

  • 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

Abstract

This study was carried out to evaluate the effects of a Huaier polysaccharide (TP-1) on the tumor growth and immune function in hepatocellular carcinoma (HCC) H22-based mouse in vivo. Results showed that TP-1 was capable of repressing transplanted H22 solid hepatic tumor cell growth in vivo, prolonging the live time of mice bearing ascetic H22 tumors, and repressing the pulmonary metastasis of H22-bearing mice. Moreover, the relative weight of immune organ (spleen and thymus) and lymphocyte proliferation were improved after TP-1 treatment. Furthermore, the treatment with TP-1 could promote immune-stimulating serum cytokines, such as IL-2 and IFN-γ, but inhibit immune-suppressing serum cytokines IL-10 secretion in H22-bearing mice. Besides, the percentage of CD4+ T cells and NK cells was increased, whereas the number of CD8+ T cells decreased in tumor-bearing mice following TP-1 administration. In addition, this compound displayed little toxic effects to major organ of tumor-bearing mice at the therapeutic dose, such as the liver and kidney. This experimental finding suggested that TP-1 exhibited prominent antitumor activities in vivo via enhancement of host immune system function in H22 tumor-bearing mice. This product could be developed individually as a safe and potent biological response modifier for HCC therapy.

Keywords

Huaier polysaccharide Antitumor Metastasis 

Notes

Acknowledgments

This research is funded by 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

None

References

  1. 1.
    Yang JD, Roberts LR. Hepatocellular carcinoma: a global view. Nat Rev Gastroenterol Hepatol. 2010;7:448–58.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Linnemann U, Schimanski CC, Gebhardt C, Berger MR. Prognostic value of disseminated colorectal tumor cells in the liver: results of follow-up examinations. Int J Colorectal Dis. 2004;19:380–6.CrossRefPubMedGoogle Scholar
  3. 3.
    Parkin DM, Pisani P, Ferlay J. Estimates of worldwide incidence of eighteen major cancers in 1985. Int J Cancer. 1993;54:594–606.CrossRefPubMedGoogle Scholar
  4. 4.
    Yuan SL, Wei YQ, Wang XJ, Xiao F, Li SF, Zhang J. Growth inhibition and apoptosis induction of tanshinone II-A on human hepatocellular carcinoma cells. World J Gastroenterol. 2004;10:2024–8.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118–27.CrossRefPubMedGoogle Scholar
  6. 6.
    Parkin DM, Bray F, Ferlay J. Global cancer statistics CA. Cancer J Clin. 1999;55:74–108.CrossRefGoogle Scholar
  7. 7.
    Coradini D, Zorzet S, Rossin R, Scarlata I, Pellizzaro C, Turrin C, et al. Inhibition of hepatocellular carcinomas in vitro and hepatic metastases in vivo in mice by the histone deacetylase inhibitor HA-But. Clin Cancer Res. 2004;10:4822–30.CrossRefPubMedGoogle Scholar
  8. 8.
    Shu G, Mi X, Cai J, Zhang X, Yin W, Yang X, et al. Brucine, an alkaloid from seeds of Strychnos nux-vomica Linn., represses hepatocellular carcinoma cell migration and metastasis: the role of hypoxia inducible factor 1 pathway. Toxicol Lett. 2013;222:91–101.CrossRefPubMedGoogle Scholar
  9. 9.
    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
  10. 10.
    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
  11. 11.
    Wasser S. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl Microbiol Biotechnol. 2003;60:258–74.Google Scholar
  12. 12.
    Staub AM. Removal of protein-Sevag method. Methods in Carbohydr Chem. 1965;5:5–6.Google Scholar
  13. 13.
    Zhu BD, Yuan SJ, Zhao QC, Li X, Li Y, Lu QY. Antitumor effect of Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, combined with cytotoxic agent on murine hepatocellular carcinoma. World J Gastroenterol. 2005;11:1382–6.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Li H, Sun M, Xu J, Li H, Zang M, Cui Y. Immunological response in H22 transplanted mice undergoing Aconitum coreanum polysaccharide treatment. Int J Biol Macromol. 2013;55:295–300.CrossRefPubMedGoogle Scholar
  15. 15.
    Zhang Y, Yu G, Wang D, Hu Y, Lei W. ERK1/2 activation plays important roles in the opposite effects of Trichostatin A in non-cancer and cancer cells. Toxicon. 2011;57:932–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Ooi VEC, Liu F. Immunomodulation and anticancer activity of polysaccharide protein complexes. Curr Med Chem. 2000;7:715–29.CrossRefPubMedGoogle Scholar
  17. 17.
    Singh SS, Haldar C, Rai S. Melatonin and differential effect of L-thyroxine on immune system of Indian tropical bird, Perdicula asiatica. Gen Comp Endocrinol. 2006;145:215–221.Google Scholar
  18. 18.
    Fu J, Fu J, Yuan J, Zhang N, Gao B, Fu G, et al. Anti-diabetic activities of Acanthopanax senticosus polysaccharide (ASP) in combination with metformin. Int J Biol Macromol. 2012;5:619–23.CrossRefGoogle Scholar
  19. 19.
    Zeng G, Ju Y, Shen H, Zhou N, Huang L. Immunopontentiating activities of the purified polysaccharide from evening primrose in H22 tumor-bearing mice. Int J Biol Macromol. 2013;52:280–5.CrossRefPubMedGoogle Scholar
  20. 20.
    O'Garra A, Arai N. The molecular basis of T helper 1 and T helper 2 cell differentiation. Trends Cell Biol. 2000;10:542–50.CrossRefPubMedGoogle Scholar
  21. 21.
    Wang N, Yang J, Lu J, Qiao Q, Wu T, Du X, et al. A polysaccharide from Salvia miltiorrhiza Bunge improves immune function in gastric cancer rats. Carbohyd Polym. 2014;111:47–55.CrossRefGoogle Scholar
  22. 22.
    Gerloni M, Zanetti M. CD4 T cells in tumor immunity. Springer Semin Immunopathol. 2005;27:37–48.CrossRefPubMedGoogle Scholar
  23. 23.
    Brunda MJ, Luistro L, Warrier RR, Wright RB, Hubbard BR, Murphy M, et al. Antitumor and antimetastatic activity of interleukin-12 against murine tumors. J Exp Med. 1993;178:1223–30.CrossRefPubMedGoogle Scholar
  24. 24.
    Shen H, Tang G, Zeng G, Yang Y, Cai X, Li D, et al. Purification and characterization of an antitumor polysaccharide from Portulaca oleracea L. Carbohydr Polym. 2013;93:395–400.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

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