Advertisement

Tumor Biology

, Volume 35, Issue 9, pp 9079–9083 | Cite as

Establishment of experimental implantation tumor models of hepatocellular carcinoma in Wistar rats

  • Yi Jin
  • Dayue Tong
  • Junjie Shen
  • Jianyong Yang
  • Jiaping Li
Research Article

Abstract

Our aims were to investigate and establish simple and reliable implanted hepatocellular carcinoma (HCC) models in Wistar rats. Concentrated suspensions of CBRH-7919 cancer cell lines were injected subcutaneously into the scapular regions of nude mice. The developing tumor tissues were then implanted into the livers of 45 adult Wistar rats. Dexamethasone (2.5 mg/day) was injected intramuscularly daily for 1 week preoperatively and 2 weeks postoperatively. After 4 weeks of implantation, ultrasonography and nuclear magnetic resonance imaging (MRI) were performed to identify model rats with liver tumor growth and to analyze the growth and characteristics of the tumors. Five of these model rats were then sacrificed, and the tumors were removed from the liver for pathological examination. Three rats died during the operation; among the remaining 42 rats, 36 possessed a total of 43 liver tumors. The success rate of tumor implantation was 85.7 % (36/42), and the diameters of the tumors ranged from 5 to 10 mm. All tumor specimens were confirmed to be HCC by pathological examination. This study provides a new approach for establishing implanted HCC models in Wistar rats, which can be used for studying numerous biological features of HCC.

Keywords

Hepatocellular carcinoma Wistar rat CBRH-7919 cell lines Animal models 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (Nos. 81171441, 81301694, 81371653), the Science and Technology Program of Guangdong Province (No. 2012B060300009), the Natural Science Foundation of Guangdong Province (Nos. S2012020010904, 7001663, S2011010004247), and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (No. 20111139).

Conflicts of interest

None

References

  1. 1.
    Crissien AM, Frenette C. Current management of hepatocellular carcinoma. Gastroenterol Hepatol (N Y). 2014;10:153–61.Google Scholar
  2. 2.
    Kim HY, Park JW. Clinical trials of combined molecular targeted therapy and locoregional therapy in hepatocellular carcinoma: past, present, and future. Liver Cancer. 2014;3:9–17.PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Rani B, Cao Y, Malfettone A, Tomuleasa C, Fabregat I, Giannelli G. Role of the tissue microenvironment as a therapeutic target in hepatocellular carcinoma. World J Gastroenterol. 2014;20:4128–40.PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Singal AG, Pillai A, Tiro J. Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis. PLoS Med. 2014;11:e1001624.PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Kubo S, Takemura S, Sakata C, Urata Y, Uenishi T. Adjuvant therapy after curative resection for hepatocellular carcinoma associated with hepatitis virus. Liver Cancer. 2013;2:40–6.PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Liao R, Wu H, Yi Y, Wang JX, Cai XY, He HW, et al. Clinical significance and gene expression study of human hepatic stellate cells in HBV related-hepatocellular carcinoma. J Exp Clin Cancer Res. 2013;32:22.PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Cariani E, Pilli M, Zerbini A, Rota C, Olivani A, Zanelli P, et al. HLA and killer immunoglobulin-like receptor genes as outcome predictors of hepatitis C virus-related hepatocellular carcinoma. Clin Cancer Res. 2013;19:5465–73.CrossRefPubMedGoogle Scholar
  8. 8.
    Nishikawa H, Arimoto A, Wakasa T, Kita R, Kimura T, Osaki Y. Comparison of clinical characteristics and survival after surgery in patients with non-B and non-C hepatocellular carcinoma and hepatitis virus-related hepatocellular carcinoma. J Cancer. 2013;4:502–13.PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Zhao GJ, Xu LX, Chu ES, Zhang N, Shen JY, Damirin A, et al. Establishment of an orthotopic transplantation tumor model of hepatocellular carcinoma in mice. World J Gastroenterol. 2012;18:7087–92.PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Wu L, Tang ZY, Li Y. Experimental models of hepatocellular carcinoma: developments and evolution. J Cancer Res Clin Oncol. 2009;135:969–81.CrossRefPubMedGoogle Scholar
  11. 11.
    Heindryckx F, Colle I, Van Vlierberghe H. Experimental mouse models for hepatocellular carcinoma research. Int J Exp Pathol. 2009;90:367–86.PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Newell P, Villanueva A, Friedman SL, Koike K, Llovet JM. Experimental models of hepatocellular carcinoma. J Hepatol. 2008;48:858–79.PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Sánchez A, Fabregat I. Genetically modified animal models recapitulating molecular events altered in human hepatocarcinogenesis. Clin Transl Oncol. 2009;11:208–14.CrossRefPubMedGoogle Scholar
  14. 14.
    Teoh NC, Dan YY, Swisshelm K, Lehman S, Wright JH, Haque J, et al. Defective DNA strand break repair causes chromosomal instability and accelerates liver carcinogenesis in mice. Hepatology. 2008;47:2078–88.CrossRefPubMedGoogle Scholar
  15. 15.
    Huynh H, Soo KC, Chow PK, Panasci L, Tran E. Xenografts of human hepatocellular carcinoma: a useful model for testing drugs. Clin Cancer Res. 2006;12:4306–14.CrossRefPubMedGoogle Scholar
  16. 16.
    Kornek M, Raskopf E, Tolba R, Becker U, Klöckner M, Sauerbruch T, et al. Accelerated orthotopic hepatocellular carcinomas growth is linked to increased expression of pro-angiogenic and prometastatic factors in murine liver fibrosis. Liver Int. 2008;28:509–18.CrossRefPubMedGoogle Scholar
  17. 17.
    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
  18. 18.
    Sun F, Tang Z, Liu K. Growth pattern and metastatic behaviour of orthotopically metastatic model of human hepatocellular carcinoma in nude mice. Zhonghua Yi Xue Za Zhi. 1995;75:673–5. 710.PubMedGoogle Scholar
  19. 19.
    Fujii E, Suzuki M, Matsubara K, Watanabe M, Chen YJ, Adachi K, et al. Establishment and characterization of in vivo human tumor models in the NOD/SCID/gamma(c)(null) mouse. Pathol Int. 2008;58:559–67.CrossRefPubMedGoogle Scholar
  20. 20.
    Zhang HJ, Chen D, Tian JM. Establishment of implanted hepatic cancer model in rats under the guidance of B-ultrasound. Chin J Med Comput Imaging. 2005;11:122–4.Google Scholar
  21. 21.
    Wang SJ, Chen B. Establishment of transplanted hepatic cancer model in SD rats. Oncol Prog. 2009;7:571–3.Google Scholar
  22. 22.
    Chu TH, Yeh HJ, Chen JMI. Establishment and some biological characteristics of a rat hepatoma cell line (CBRH-7919). Acta Biol Exp Sin. 1980;13:113–5.Google Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Yi Jin
    • 1
  • Dayue Tong
    • 2
  • Junjie Shen
    • 3
  • Jianyong Yang
    • 3
  • Jiaping Li
    • 3
  1. 1.Department of Pathology, The Third Affiliated HospitalSun Yat-Sen UniversityGuangzhouChina
  2. 2.Department of Forensic Medicine, ZhongShan Medical SchoolSun Yat-Sen UniversityGuangzhouChina
  3. 3.Department of Interventional Oncology, The First Affiliated HospitalSun Yat-Sen UniversityGuangzhouChina

Personalised recommendations