Effects of Tyrosine Kinase Inhibitors and CXCR4 Antagonist on Tumor Growth and Angiogenesis in Rat Glioma Model: MRI and Protein Analysis Study

• Published in: Translational oncology 2013-12, Vol.6 (6), p.660-669
• Main Authors: Ali, Meser M, Kumar, Sanath, Shankar, Adarsh, Varma, Nadimpalli R.S, Iskander, A.S.M, Janic, Branislava, Chwang, Wilson B, Jain, Rajan, Babajeni-Feremi, Abbas, Borin, Thaiz F, Bagher-Ebadian, Hassan, Brown, Stephen L, Ewing, James R, Arbab, Ali S
• Format: Article
• Language: English
• Subjects: Oncology
• ISSN: 1936-5233
• DOI: 10.1593/tlo.13559

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.