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Abstract
Purpose
The purpose of this study was to evaluate the effect of 2-deoxy-D-glucose (2-DG) on the spatial distribution of the genetic expression of key elements involved in angiogenesis, hypoxia, cellular metabolism, and apoptosis in LHBETATAG retinal tumors.
Methods
The right eye of each LHBETATAG transgenic mouse (n = 24) was treated with either two or six subconjunctival injections of 2-DG (500 mg/kg) or saline control at 16 weeks of age. A gene expression array analysis was performed on five different intratumoral regions (apex, center, base, anterior-lateral, and posterior-lateral) using Affymetrix GeneChip Mouse Gene 1.0 ST arrays. To test for treatment effects of each probe within each region, a two-way analysis of variance was used.
Results
Significant differences between treatment groups (ie, 0, 2, and 6 injections) were found as well as differences among the five retinal tumor regions evaluated (P < 0.01). More than 100 genes were observed to be dysregulated by ≥2-fold difference in expression between the three treatment groups, and their dysregulation varied across the five regions assayed. Several genes involved in pathways important for tumor cell growth (ie, angiogenesis, hypoxia, cellular metabolism, and apoptosis) were identified.
Conclusions
2-DG was found to significantly alter the gene expression in LHBETATAG retinal tumor cells according to their location within the tumor as well as the treatment schedule. 2-DG’s effects on genetic expression found here correlate with previous reported results on varied processes involved in its in vitro and in vivo activity in inhibiting tumor cell growth.
Acknowledgments
Supported by NIH center grant R01 EY013629, R01 EY12651, and P30 EY014801; by the American Cancer Society, Sylvester Comprehensive Cancer Center; and by an unrestricted grant to the University of Miami from Research to Prevent Blindness, Inc. L Nathanson, T Koru-Sengul, and J Clarke had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Disclosure
The authors report no conflicts of interest in this work.