Skip to main content

Advertisement

SpringerLink
Log in

Validation of Bevacizumab Therapy Effect on Colon Cancer Subtypes by Using Whole Body Imaging in Mice

  • Research Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Purpose

Preclinical imaging offers a useful tool for monitoring cancer biological behavior and therapy in vivo without the necessity of animal surgery. The following paper describes our examination of tumor progress and anti-angiogenic therapy with Bevacizumab on colon cancer subtypes (SW480 and SW620) by using different non-invasive real-time in vivo imaging techniques.

Procedures

Color Doppler ultrasound imaging (CDUI) was used to observe the formation of new blood vessels; a homemade fluorescence reflectance imaging (FRI) apparatus was mainly used to test the difference in VEGFR2 expression between the tumor subtypes. Briefly, 15 Balb/c nude mice bearing subcutaneous SW480 and SW620 xenografts were randomly divided into Control and Drug groups. Bevacizumab treatment lasted for 3 weeks. All images were captured pre- and post-treatment. At the end of experiment, all mice were euthanized, and tumor tissue was collected and analyzed by immunohistochemical staining.

Results

Expression of VEGFR2 was found to be slightly (10 %) but significantly higher for the SW620 cells than for SW480 cells. In addition, SW620 has shown to be more vascularized than SW480 subtype. After 3-week Bevacizumab therapy, no blood vessels were found within 83 % of SW620, while it was 67 % in SW480; the increase of SW620 tumor volume post-treatment was only 3.17-fold compared with the tumor volume pre-treatment, and 4.51-fold higher in SW480.

Conclusion

Our data suggest that SW480 and SW620 cell lines respond differently to Bevacizumab therapy in vivo. Because of higher vascularization, and subsequently higher reduction by drug of new blood vessels and tumor growth rate, xenografts derived from the metastatic SW620 cell line have a better chance of being successfully treated with Bevacizumab compared with those derived from the primary tumor SW480 cell line.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.

Similar content being viewed by others

Abbreviations

CDUI:

Color Doppler ultrasound imaging

FRI:

Fluorescence reflectance imaging

NBV:

New blood vessels

CRC:

Colorectal cancer

IHC:

Immunohistochemistry

References

  1. Leibovitz A, Stinson JC, McCombs WB et al (1976) Classification of human colorectal adenocarcinoma cell lines. Cancer Res 36:4562–4569

    CAS  PubMed  Google Scholar 

  2. Hewitt R, McMarlin A, Kleiner D et al (2000) Validation of a model of colon cancer progression. J Pathol 192:446–454

    Article  CAS  PubMed  Google Scholar 

  3. Wang H, Jinming Z, Jiahe T et al (2009) Using dual-tracer PET to predict the biologic behavior of human colorectal cancer. J Nucl Med 50:1857–1864

    Article  CAS  PubMed  Google Scholar 

  4. Sukhdeo K, Paranmban RI, Vidal JG et al (2013) Multiplex flow cytometry barcoding and antibody arrays identify surface antigen profiles of primary and metastatic colon cancer cell lines. PLoS One 8:e53015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mousa L, Salem M, Mikhail S (2015) Biomarkers of angiogenesis in colorectal cancer. Biomarkers in Cancer 7(s1):13–19

    PubMed  PubMed Central  Google Scholar 

  6. Wang H, Liu B, Tian J et al (2010) Monitoring early responses to irradiation with dual-tracer micro-PET in dual-tumor bearing mice. World J Gastroenterol 16(43):5416–5423

    Article  PubMed  PubMed Central  Google Scholar 

  7. Heenan SD (2004) Magnetic resonance imaging in prostate cancer. Nat Publ Group 7:282–288

    CAS  Google Scholar 

  8. Cherry S (2006) Multimodality in vivo imaging systems: twice the power or double the trouble? Annu Rev Biomed Eng 8:35–62

    Article  CAS  PubMed  Google Scholar 

  9. Dort M, Rehemtulla A, Ross B (2008) PET and SPECT imaging of tumor biology: new approaches towards oncology drug discovery and development. Curr Comput Aided Drug Des 4(1):46–45

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ji S, Zheng Y, Shao G (2013) Integrin αvβ3–targeted radiotracer 99mTc-3P-RGD2Useful for noninvasive monitoring of breast tumor response to antiangiogenic linifanib therapy but not anti-integrin αvβ3RGD2 therapy. Theranostics 3(11):816–830

    Article  PubMed  PubMed Central  Google Scholar 

  11. Vuletic I, Liu J, Wu H et al (2015) Establishment of an mKate2-expressing cell line for non-invasive real-time breast cancer in vivo imaging. Mol Imaging Biol 17:811–818

    Article  CAS  PubMed  Google Scholar 

  12. Huang D, Lan H, Liu et al (2015) Anti-angiogenesis or pro-angiogenesis for cancer treatment: focus on drug distribution. Int J Clin Exp Med 8(6):8369–8376

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Hasan M, Ho S, Owen D et al (2011) Inhibition of VEGF induces cellular senescence in colorectal cancer cells. Int J Cancer 129:2115–2123

    Article  CAS  PubMed  Google Scholar 

  14. Wang Y, Fei D, Vanderlaan M et al (2004) Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro. Angiogenesis 7:335–345

    Article  CAS  PubMed  Google Scholar 

  15. Kim T, Landen C, Lin Y et al (2009) Combined anti-angiogenic therapy against VEGF and integrin alphaVbeta3 in an orthotopic model of ovarian cancer. Cancer Biol Ther 8(23):2263–2272

    Article  PubMed  PubMed Central  Google Scholar 

  16. Thaker A, Razjouyan F, Woods D et al (2012) Combination therapy of radiofrequency ablation and bevacizumab monitored with power Doppler ultrasound in a murine model of hepatocellular carcinoma. Int J Hyperth 28(8):766–775

    Article  CAS  Google Scholar 

  17. Zhu H, Li Z, Mao S et al (2011) Antitumor effect of sFlt-1 gene therapy system mediated by Bifidobacterium Infantis on Lewis lung cancer in mice. Cancer Gene Ther 18:884–896

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Roskoski RJ (2008) VEGF receptor protein–tyrosine kinases: structure and regulation. Biochem Biophys Res Commun 375:287–291

    Article  CAS  PubMed  Google Scholar 

  19. Hao Y, Yang J, Yin S et al (2014) The synergistic regulation of VEGF-mediated angiogenesis through miR-190 and target genes. RNA 20(8):1328–1336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yancopoulos G, Davis S, Gale N et al (2000) Vascular-specific growth factors and blood vessel formation. Nature 407(6801):242–248

    Article  CAS  PubMed  Google Scholar 

  21. Saif MS (2013) Anti-VEGF agents in metastatic colorectal cancer (mCRC): are they all alike? Cancer Manag Res 5:103–111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. He K, Cui B, Li G et al (2012) The effect of anti-VEGF drugs (bevacizumab and aflibercept) on the survival of patients with metastatic colorectal cancer (mCRC). OncoTargets and Therapy 5:59–65

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We acknowledge the financial support by the National Key Instrumentation Development Project (No. 2011YQ030114), the Natural Science Foundation of China (No. 81421004), and the Beijing Natural Science Foundation (No. 7162113). We would like also to thank Prof. Ming Fan and Prof. Lingling Zhu from the Institute of Basic Medical Sciences (Beijing 100850, China) for their assistance and advice regarding our hypoxia experiment.

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, College of Engineering, Peking University, No. 5 Yiheyuan Road, Beijing, 100871, China

    Ivan Vuletic, Kedi Zhou, Xiangxi Meng, Sihao Zhu, Yichen Ding, Hongfang Sun & Qiushi Ren

  2. Laboratory Animal Center, Peking University, No. 5 Yiheyuan Road, Beijing, 100871, China

    Hui Li, Huichen Bai & Jun Li

Authors
  1. Ivan Vuletic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kedi Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Huichen Bai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiangxi Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sihao Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yichen Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hongfang Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Qiushi Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Hongfang Sun or Qiushi Ren.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interests.

Electronic Supplementary Material

.

ESM 1

(PDF 662 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vuletic, I., Zhou, K., Li, H. et al. Validation of Bevacizumab Therapy Effect on Colon Cancer Subtypes by Using Whole Body Imaging in Mice. Mol Imaging Biol 19, 847–856 (2017). https://doi.org/10.1007/s11307-017-1048-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-017-1048-z

Key words

Search

Navigation