Effects of tyrosine kinase inhibitors and CXCR4 antagonist on tumor growth and angiogenesis in rat glioma model: MRI and protein analysis study

Meser M. Ali, Sanath Kumar, Adarsh Shankar, Nadimpalli R.S. Varma, A. S.M. Iskander, Branislava Janic, Wilson B. Chwang, Rajan Jain, Abbas Babajeni-Feremi, Thaiz Ferraz Borin, Hassan Bagher-Ebadian, Stephen L. Brown, James R. Ewing, Ali Syed Arbab

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The aim of the study was to determine the antiangiogenic efficacy of vatalanib, sunitinib, and AMD3100 in an animal model of human glioblastoma (GBM) by using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and tumor protein expression analysis. Orthotopic GBM-bearing animals were randomly assigned either to control group or vatalanib, sunitinib, and AMD3100 treatment groups. Following 2 weeks of drug treatment, tumor growth and vascular parameters were measured using DCE-MRI. Expression of different angiogenic factors in tumor extracts was measured using a membrane-based human antibody array kit. Tumor angiogenesis and invasion were determined by immunohistochemistry. DCE-MRI showed a significant increase in tumor size after vatalanib treatment. AMD3100-treated group showed a significant decrease in a number of vascular parameters determined by DCE-MRI. AMD3100 significantly decreased the expression of different angiogenic factors compared to sunitinib or vatalanib; however, there were no significant changes in vascular density among the groups. Sunitinib-treated animals showed significantly higher migration of the invasive cells, whereas in both vatalanib- and AMD3100-treated animals the invasive cell migration distance was significantly lower compared to that of control. Vatalanib and sunitinib resulted in suboptimal therapeutic effect, but AMD3100 treatment resulted in a significant reduction in tumor growth, permeability, interstitial space volume, and invasion of tumor cells in an animal model of GBM.

Original languageEnglish (US)
Pages (from-to)660-669
Number of pages10
JournalTranslational Oncology
Volume6
Issue number6
DOIs
StatePublished - Dec 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Ali, M. M., Kumar, S., Shankar, A., Varma, N. R. S., Iskander, A. S. M., Janic, B., Chwang, W. B., Jain, R., Babajeni-Feremi, A., Borin, T. F., Bagher-Ebadian, H., Brown, S. L., Ewing, J. R., & Arbab, A. S. (2013). Effects of tyrosine kinase inhibitors and CXCR4 antagonist on tumor growth and angiogenesis in rat glioma model: MRI and protein analysis study. Translational Oncology, 6(6), 660-669. https://doi.org/10.1593/tlo.13559