Drug/diet synergy for managing malignant astrocytoma in mice: 2-deoxy-D-glucose and the restricted ketogenic diet.
Drug/diet synergy for managing malignant astrocytoma in mice: 2-deoxy-D-glucose and the restricted ketogenic diet.
复制标题
DOI：
10.1186/1743-7075-5-33
复制
发表时间：
2008-11-25
影响因子：
4.5
通讯作者：
Seyfried TN
中科院分区：
文献类型：
--
作者：
Marsh J;Mukherjee P;Seyfried TN
星形细胞瘤在很大程度上依赖于糖酵解来满足其生长和存活的生物能量需求。靶向糖酵解的治疗可以潜在地控制星形细胞瘤的生长和进展。高脂肪/低碳水化合物生酮饮食（KD-R）的饮食限制减少糖酵解，并有效地管理实验小鼠和人类星形细胞瘤。不可代谢的葡萄糖类似物2-脱氧-D-葡萄糖（2-DG）是一种有效的糖酵解抑制剂，可以模拟体外和体内能量限制的作用，但当以大于200 mg/kg的剂量给药时也会产生不良反应。目的是确定低剂量的2-DG是否可以与KD-R协同作用，以更好地控制CT-2A恶性小鼠星形细胞瘤的生长。补充低剂量2-DG（25 mg/kg）的KD-R的治疗效果在成年C57 BL/6 J小鼠中进行了检查，该小鼠带有原位生长的同基因CT-2A恶性星形细胞瘤。小鼠在肿瘤植入后的前3天喂食标准非限制性饮食，然后将其分成四个饮食组之一，喂食不受限制量的标准啮齿动物饮食（SD-UR）或含或不含2-DG的KD-R 10天。KD-R仅限于减轻体重约20%。2-DG在肿瘤植入后6天开始，并持续7天。切除脑肿瘤并称重。在饮食处理期间（第3-13天），SD-UR和SD-UR+2-2DG小鼠组的能量摄入、体重和CT-2A肿瘤重量相似。KD-R组和KD-R+2-DG组的肿瘤重量分别比SD-UR组低约48%和80%。KD-R组小鼠的健康和活力优于KD-R+2-DG组。补充2-DG的KD-R小鼠组的星形细胞瘤生长比接受饮食限制或仅接受2-DG的小鼠组减少得更多，表明药物和饮食之间存在协同相互作用。结果表明，与抑制糖酵解的药物联合使用时，限制生酮饮食对恶性星形细胞瘤的治疗可能会得到加强。
Astrocytomas are largely dependent on glycolysis to satisfy their bioenergetic requirements for growth and survival. Therapies that target glycolysis can potentially manage astrocytoma growth and progression. Dietary restriction of the high fat/low carbohydrate ketogenic diet (KD-R) reduces glycolysis and is effective in managing experimental mouse and human astrocytomas. The non-metabolizable glucose analogue, 2-deoxy-D-glucose (2-DG), is a potent glycolytic inhibitor that can mimic effects of energy restriction both in vitro and in vivo, but can also produce adverse effects when administered at doses greater than 200 mg/kg. The goal here was to determine if low doses of 2-DG could act synergistically with the KD-R to better manage growth of the CT-2A malignant mouse astrocytoma. The therapeutic effect of a KD-R supplemented with a low dose of 2-DG (25 mg/kg) was examined in adult C57BL/6J mice bearing the syngeneic CT-2A malignant astrocytoma grown orthotopically. Mice were fed the standard unrestricted diet for the first 3 days after tumor implantation prior to their separation into one of four diet groups fed either a standard rodent diet in unrestricted amounts (SD-UR) or a KD-R with or without 2-DG for 10 days. The KD-R was restricted to reduce body weight by about 20%. 2-DG was initiated 6 days after tumor implantation and was continued for 7 days. Brain tumors were excised and weighed. Energy intake, body weights, and CT-2A tumor weights were similar in the SD-UR and the SD-UR+2-2DG mouse groups over the dietary treatment period (days 3–13). Tumor weights were about 48% and 80% lower in the KD-R and in the KD-R+2-DG groups, respectively, than in the SD-UR group. Mouse health and vitality was better in the KD-R group than in the KD-R+2-DG group. Astrocytoma growth was reduced more in the KD-R mouse group supplemented with 2-DG than in the mouse groups receiving either dietary restriction or 2-DG alone, indicating a synergistic interaction between the drug and the diet. The results suggest that management of malignant astrocytoma with restricted ketogenic diets could be enhanced when combined with drugs that inhibit glycolysis.
登录
查看更多内容
影响因子：
4.7
作者：
FLAVIN, HJ;WIERASZKO, A;SEYFRIED, TN
通讯作者：
SEYFRIED, TN
影响因子：
3.1
作者：
Singh, DH;Banerji, AK;Jain, V
通讯作者：
Jain, V
影响因子：
8.8
作者：
Mukherjee, P;El-Abbadi, M M;Kasperzyk, J L;Ranes, M K;Seyfried, T N
通讯作者：
Seyfried, T N
影响因子：
--
作者：
Lowry, JK;Snyder, JJ;Lowry, PW
通讯作者：
Lowry, PW
影响因子：
4.5
作者：
Seyfried, Thomas N;Mukherjee, Purna
通讯作者：
Mukherjee, Purna