Skip to main content
Download PDF

Retrospective growth kinetics and radiosensitivity analysis of various human xenograft models

Laboratory Animal Research volume 32, pages 187–193 (2016)Cite this article

Abstract

The purpose of this study was to delineate the various factors that affect the growth characteristics of human cancer xenografts in nude mice and to reveal the relationship between the growth characteristics and radiosensitivity. We retrospectively analyzed 390 xenografts comprising nine different human cancer lines grown in nude mice used in our institute between 2009 and 2015. Tumor growth rate (TCR) was calculated using exponential growth equations. The relationship between the TCR of xenografts and the proliferation of the cells in vitro was examined. Additionally, we examined the correlations between the surviving fractions of cells after 2 Cy irradiation in vitro and the response of the xenograft to radiation. The TCR of xenografts was positively related to the proliferation of the cells in vitro (rp=0.9714, p < 0.0001), whereas it was independent of the histological type of the xenografts. Radiation-induced suppression of the growth rate (T/C%) of xenografts was positively related to the radiosensitivity of the cells in vitro (SF2; rp=0.8684, p=0.0284) and TCR (rp=0.7623, p=0.0780). The proliferation of human cancer cells in vitro and the growth rate of xenografts were positively related. The radiosensitivity of cancer cells, as judged from the SF2 values in vitro, and the radiation-induced suppression of xenograft growth were positively related. In conclusion, the growth rate of human xenografts was independent of histological type and origin of the cancer cells, and was positively related to the proliferation of the cancer cells in vitro.

References

  1. Ruggeri BA, Camp F, Miknyoczki S. Animal models of disease: pre-clinical animal models of cancer and their applications and utility in drug discovery. Biochem Pharmacol 2014; 87(1): 150–161.

    Article  CAS  Google Scholar 

  2. Wong H, Choo EF, Alicke B, Ding X, La H, McNamara E, Theil FP, Tibbitts J, Friedman LS, Hop CE, Gould SE. Antitumor activity of targeted and cytotoxic agents in murine subcutaneous tumor models correlates with clinical response. Clin Cancer Res 2012; 18(14): 3846–3855.

    Article  CAS  Google Scholar 

  3. Voskoglou-Nomikos T, Pater JL, Seymour L. Clinical predictive value of the in vitro cell line, human xenograft, and mouse allograft preclinical cancer models. Clin Cancer Res 2003; 9(11):4227–4239.

    PubMed  Google Scholar 

  4. Sausville EA, Burger AM. Contributions of human tumor xenografts to anticancer drug development. Cancer Res 2006; 66(7): 3351–3354.

    Article  CAS  Google Scholar 

  5. Morton CL, Houghton PJ. Establishment of human tumor xenografts in immunodeficient mice. Nat Protoc 2007; 2(2): 247–250.

    Article  CAS  Google Scholar 

  6. Baserga R. The relationship of the cell cycle to tumor growth and control of cell division: A review. Cancer Res 1965; 25: 581–595.

    CAS  PubMed  Google Scholar 

  7. Schabel FM Jr. The use of tumor growth kinetics in planning “curative” chemotherapy of advanced solid tumors. Cancer Res 1969; 29(12): 2384–2389.

    PubMed  Google Scholar 

  8. Frindel E, Malaise EP, Alpen E, Tubiana M. Kinetics of cell proliferation of an experimental tumor. Cancer Res 1967; 27(6): 1122–1131.

    CAS  PubMed  Google Scholar 

  9. Bru A, Albertos S, Luis Subiza J, Garcia-Asenjo IL, Bru I. The universal dynamics of tumor growth. Biophys J 2003; 85(5): 2948–2961.

    Article  CAS  Google Scholar 

  10. Vaupel P, Kallinowski F, Okunieff P. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res 1989; 49(23): 6449–6465.

    CAS  PubMed  Google Scholar 

  11. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 2005; 23(5): 1011–1027.

    Article  CAS  Google Scholar 

  12. Brown JM, Giaccia AJ. The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res 1998; 58(7): 1408–1416.

    CAS  PubMed  Google Scholar 

  13. Jeong YK, Kim MS, Lee JY, Kim EH, Ha H. Metformin Radiosensitizes p53-Deficient Colorectal Cancer Cells through Induction of G2/M Arrest and Inhibition of DNA Repair Proteins. PLoS One. 2015; 10(11): e0143596.

    Article  Google Scholar 

  14. Lee JM, Bernstein A. p53 mutations increase resistance to ionizing radiation. Proc Natl Acad Sci USA 1993; 90(12): 5742–5746.

    Article  CAS  Google Scholar 

  15. Chang L, Graham PH, Hao J, Ni J, Bucci J, Cozzi PJ, Kearsley JH, Li Y. PI3K/Akt/mTOR pathway inhibitors enhance radiosensitivity in radioresistant prostate cancer cells through inducing apoptosis, reducing autophagy, suppressing NHEJ and HR repair pathways. Cell Death Dis 2014; 5: e1437.

    Article  CAS  Google Scholar 

  16. Bussink J, van der Kogel AJ, Kaanders JH. Activation of the PI3-K/AKT pathway and implications for radioresistance mechanisms in head and neck cancer. Lancet Oncol 2008; 9(3): 288–296.

    Article  CAS  Google Scholar 

  17. Li HF, Kim JS, Waldman T. Radiation-induced Akt activation modulates radioresistance in human glioblastoma cells. Radiat Oncol 2009; 4: 43.

    Article  Google Scholar 

  18. Moeller BJ, Cao Y, Li CY, Dewhirst MW. Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules. Cancer Cell 2004; 5(5): 429–441.

    Article  CAS  Google Scholar 

  19. Semenza GL. Intratumoral hypoxia, radiation resistance, and HIF-1. Cancer Cell 2004; 5(5): 405–406.

    Article  CAS  Google Scholar 

  20. Hockel M, Vaupel P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst 2001; 93(4): 266–276.

    Article  CAS  Google Scholar 

  21. Hill RP, Bristow RG, Fyles A, Koritzinsky M, Milosevic M, Wouters BG. Hypoxia and Predicting Radiation Response. Semin Radiat Oncol 2015; 25(4): 260–272.

    Article  Google Scholar 

  22. Moeller BJ, Dewhirst MW. HIF-1 and tumour radiosensitivity. Br J Cancer 2006; 95(1): 1–5.

    Article  CAS  Google Scholar 

  23. Kim JH, Evans TC. Effects of X-irradiation on the mitotic cycle of ehrlich ascites tumor cells. Radiat Res 1964; 21: 129–143.

    Article  CAS  Google Scholar 

  24. Breur K. Growth rate and radiosensitivity of human tumours. II. Radiosensitivity of human tumours. Eur J Cancer 1966; 2(2): 173–188.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Radiation Non-clinical Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), 75 Nowonro, Nowon-gu, Seoul, 01812, Korea

    Ji Young Lee & Youn Kyoung Jeong

  2. Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences (KIRAMS), 75 Nowonro, Nowon-gu, Seoul, 01812, Korea

    Mi-Sook Kim

  3. Division of Heavy Ion Clinical Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea

    Eun Ho Kim

  4. Department of Biosystems Engineering, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea

    Ji Young Lee & Namhyun Chung

Authors
  1. Ji Young Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mi-Sook Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eun Ho Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Namhyun Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Youn Kyoung Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Mi-Sook Kim or Youn Kyoung Jeong.

Rights and permissions

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://doi.org/creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, J.Y., Kim, MS., Kim, E.H. et al. Retrospective growth kinetics and radiosensitivity analysis of various human xenograft models. Lab Anim Res 32, 187–193 (2016). https://doi.org/10.5625/lar.2016.32.4.187

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.5625/lar.2016.32.4.187

Keywords

Laboratory Animal Research

ISSN: 2233-7660