In many tumors, cancer cells take up large quantities of glucose and metabolize it into lactate, even in the presence of sufficient oxygen to support oxidative metabolism. It has been hypothesized that this malignant metabolic phenotype supports cancer growth and metastasis, and that reversal of this so-called “Warburg effect” may selectively harm cancer cells. Conversion of glucose to lactate can be reduced by ablation or inhibition of lactate dehydrogenase (LDH), the enzyme responsible for conversion of pyruvate to lactate at the endpoint of glycolysis. Recently developed inhibitors of LDH provide new opportunities to investigate the role of this metabolic pathway in cancer. Here we show that magnetic resonance spectroscopic imaging of hyperpolarized pyruvate and its metabolites in models of breast and lung cancer reveal that inhibition of LDH was readily visualized through reduction in label exchange between pyruvate and lactate, while genetic ablation of the LDH-A isoform alone had smaller effects. During the acute phase of LDH inhibition in breast cancer, no discernible bicarbonate signal was observed and small signals from alanine were unchanged.

中文翻译：

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用超极化丙酮酸 NMR 可视化乳酸脱氢酶 (LDH) 抑制和 LDH-A 基因消融对乳腺癌和肺癌的影响

在许多肿瘤中，癌细胞摄取大量葡萄糖并将其代谢成乳酸，即使存在足够的氧气来支持氧化代谢。据推测，这种恶性代谢表型支持癌症生长和转移，并且这种所谓的“Warburg 效应”的逆转可能会选择性地伤害癌细胞。可以通过消融或抑制乳酸脱氢酶 (LDH) 来减少葡萄糖向乳酸的转化，该酶负责在糖酵解的终点将丙酮酸转化为乳酸。最近开发的 LDH 抑制剂为研究这种代谢途径在癌症中的作用提供了新的机会。单独的 LDH-A异构体具有较小的影响。在乳腺癌 LDH 抑制的急性期，没有观察到明显的碳酸氢盐信号，丙氨酸的小信号没有变化。