Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, United States of America.
PLoS One. 2013 Jun 5;8(6):e65522. doi: 10.1371/journal.pone.0065522. Print 2013.
Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD) is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO₂T) saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease.
We used the firefly luciferase-tagged VM-M3 mouse model of metastatic cancer to compare tumor progression and survival in mice fed standard or KD ad libitum with or without HBO₂T (2.5 ATM absolute, 90 min, 3x/week). Tumor growth was monitored by in vivo bioluminescent imaging.
KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer. While HBO₂T alone did not influence cancer progression, combining the KD with HBO₂T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean survival time compared to controls.
KD and HBO₂T produce significant anti-cancer effects when combined in a natural model of systemic metastatic cancer. Our evidence suggests that these therapies should be further investigated as potential non-toxic treatments or adjuvant therapies to standard care for patients with systemic metastatic disease.
异常的癌症代谢会产生糖酵解依赖性，这可以通过降低肿瘤的葡萄糖供应来利用。生酮饮食（KD）是一种低碳水化合物、高脂肪的饮食，可降低血糖并升高血液酮体，已被证明可减缓动物和人类的癌症进展。异常的肿瘤血管生成会产生缺氧口袋，促进癌症进展，并进一步增加癌症的糖酵解依赖性。高压氧治疗（HBO₂T）用氧气使肿瘤饱和，逆转肿瘤缺氧对癌症的促进作用。由于这些无毒治疗方法利用了癌症重叠的代谢缺陷，我们在转移性疾病的自然模型中测试了它们对癌症进展的联合影响。
我们使用萤火虫荧光素酶标记的 VM-M3 小鼠转移性癌症模型，比较了自由摄入标准饮食或 KD 饮食的小鼠以及接受或不接受 HBO₂T（2.5 ATM 绝对压力，90 分钟，每周 3 次）的小鼠的肿瘤进展和生存情况。通过体内生物发光成像监测肿瘤生长。
KD 单独使用可显著降低血糖，减缓肿瘤生长，并使患有全身性转移性癌症的小鼠的平均生存时间延长 56.7%。虽然 HBO₂T 单独使用不会影响癌症进展，但将 KD 与 HBO₂T 联合使用可显著降低血糖、肿瘤生长速度，并使平均生存时间延长 77.9%，与对照组相比。
KD 和 HBO₂T 在全身性转移性癌症的自然模型中联合使用时会产生显著的抗癌作用。我们的证据表明，这些疗法应作为对患有全身性转移性疾病的患者的标准治疗的潜在无毒治疗或辅助治疗进一步研究。
