Retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LH(BETA)T(AG) retinal tumors.
Retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LH(BETA)T(AG) retinal tumors.
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DOI：
10.2147/opth.s29688
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
Lampidis TJ
中科院分区：
文献类型：
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作者：
Piña Y;Houston SK;Murray TG;Koru-Sengul T;Decatur C;Scott WK;Nathanson L;Clarke J;Lampidis TJ
本研究的目的是评估2-脱氧-d -葡萄糖（2-DG）对LHBETATAG视网膜肿瘤中血管生成、缺氧、细胞代谢和凋亡相关关键基因基因表达空间分布的影响。16周龄时，每只LHBETATAG转基因小鼠（n = 24）右眼分别接受2次或6次2-DG （500 mg/kg）结膜下注射或生理盐水对照。采用Affymetrix基因芯片小鼠基因1.0 ST阵列对5个不同的肿瘤内区域（尖端、中心、基部、前外侧和后外侧）进行基因表达阵列分析。为了检验每个探针在每个区域内的治疗效果，采用了双向方差分析。注射0、2、6组间差异有统计学意义，5个视网膜肿瘤区域间差异有统计学意义（P < 0.01）。超过100个基因被观察到失调，在三个治疗组之间的表达差异≥2倍，并且它们的失调在五个检测区域中有所不同。几个基因参与肿瘤细胞生长的重要途径（即血管生成，缺氧，细胞代谢和凋亡）被确定。发现2-DG可根据LHBETATAG视网膜肿瘤细胞在肿瘤内的位置和治疗方案显著改变其基因表达。本文发现的2-DG对基因表达的影响与先前报道的2-DG在体外和体内抑制肿瘤细胞生长的不同过程相关。
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. 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. 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. 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.