Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
Radiother Oncol. 2010 Jan;94(1):102-9. doi: 10.1016/j.radonc.2009.11.007. Epub 2009 Dec 28.
To study whether pre-therapeutic lactate or pyruvate predict for tumour response to fractionated irradiation and to identify possible coherencies between intermediates of glycolysis and expression levels of selected proteins.
Concentrations of lactate, pyruvate, glucose and ATP were quantified via bioluminescence imaging in tumour xenografts derived from 10 human head and neck squamous cell carcinoma (HNSCC) lines. Tumours were irradiated with 30 fractions within 6 weeks. Expression levels of the selected proteins in tumours were measured at the mRNA and protein level. Tumour-infiltrating leucocytes were quantified after staining for CD45.
Lactate but not pyruvate concentrations were significantly correlated with tumour response to fractionated irradiation. Lactate concentrations in vivo did not reflect lactate production rates in vitro. Metabolite concentrations did not correlate with GLUT1, PFK-L or LDH-A at the transcriptional or protein level. CD45-positive cell infiltration was low in the majority of tumours and did not correlate with lactate concentration.
Our data support the hypothesis that the antioxidative capacity of lactate may contribute to radioresistance in malignant tumours. Non-invasive imaging of lactate to monitor radiation response and testing inhibitors of glycolysis to improve outcome after fractionated radiotherapy warrant further investigations.
研究治疗前乳酸或丙酮酸是否能预测肿瘤对分割放疗的反应，并确定糖酵解中间产物与选定蛋白表达水平之间的可能相关性。
通过生物发光成像技术，在源自 10 个人类头颈部鳞状细胞癌（HNSCC）系的肿瘤异种移植中定量测定乳酸、丙酮酸、葡萄糖和 ATP 的浓度。肿瘤在 6 周内接受 30 次分割照射。在 mRNA 和蛋白水平上测量肿瘤中选定蛋白的表达水平。在对 CD45 染色后，定量肿瘤浸润的白细胞。
乳酸浓度而不是丙酮酸浓度与肿瘤对分割放疗的反应显著相关。体内的乳酸浓度并不能反映体外的乳酸生成速率。代谢物浓度与转录或蛋白水平的 GLUT1、PFK-L 或 LDH-A 均无相关性。大多数肿瘤中 CD45 阳性细胞浸润较低，与乳酸浓度无相关性。
我们的数据支持这样的假设，即乳酸的抗氧化能力可能有助于恶性肿瘤的放射抵抗。用非侵入性成像方法监测乳酸以监测放疗反应，并测试糖酵解抑制剂以改善分割放疗后的结果，这值得进一步研究。
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