Calorie restriction as an anti-invasive therapy for malignant brain cancer in the VM mouse.
Calorie restriction as an anti-invasive therapy for malignant brain cancer in the VM mouse.
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DOI：
10.1042/an20100002
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发表时间：
2010-07-23
期刊：
影响因子：
4.7
通讯作者：
Seyfried TN
中科院分区：
文献类型：
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作者：
Shelton LM;Huysentruyt LC;Mukherjee P;Seyfried TN
GBM（多形性胶质母细胞瘤）是原发性人类脑癌中最具侵袭性和侵袭性的形式。我们最近在近交 VM 小鼠品系中开发了一种新型脑癌模型，该模型与人类 GBM 具有一些共同特征。使用生物发光成像，我们测试了 CR（热量限制）减少肿瘤大小和侵袭的功效。 CR 部分通过降低循环葡萄糖水平来靶向糖酵解和快速肿瘤细胞生长。 VM-M3肿瘤细胞被植入同基因VM小鼠宿主的脑内。大约。植入后12-15天，取出大脑并对同侧和对侧半球进行成像以测量入侵肿瘤细胞的生物发光。 CR显着减少了肿瘤细胞从植入的同侧半球侵入对侧半球。 CR治疗小鼠的原发肿瘤内Ki-67染色细胞的总百分比和血管总数也显着低于随意喂养的小鼠，这表明CR具有抗增殖和抗血管生成的作用。我们的研究结果表明，VM-M3 GBM 模型是研究脑肿瘤细胞侵袭和评估治疗侵袭性脑癌的潜在治疗方法的宝贵工具。此外，我们还发现 CR 可以有效减少恶性脑肿瘤的生长和侵袭。
GBM (glioblastoma multiforme) is the most aggressive and invasive form of primary human brain cancer. We recently developed a novel brain cancer model in the inbred VM mouse strain that shares several characteristics with human GBM. Using bioluminescence imaging, we tested the efficacy of CR (calorie restriction) for its ability to reduce tumour size and invasion. CR targets glycolysis and rapid tumour cell growth in part by lowering circulating glucose levels. The VM-M3 tumour cells were implanted intracerebrally in the syngeneic VM mouse host. Approx. 12–15 days post-implantation, brains were removed and both ipsilateral and contralateral hemispheres were imaged to measure bioluminescence of invading tumour cells. CR significantly reduced the invasion of tumour cells from the implanted ipsilateral hemisphere into the contralateral hemisphere. The total percentage of Ki-67-stained cells within the primary tumour and the total number of blood vessels was also significantly lower in the CR-treated mice than in the mice fed ad libitum, suggesting that CR is anti-proliferative and anti-angiogenic. Our findings indicate that the VM-M3 GBM model is a valuable tool for studying brain tumour cell invasion and for evaluating potential therapeutic approaches for managing invasive brain cancer. In addition, we show that CR can be effective in reducing malignant brain tumour growth and invasion.