Institute of Biomedicine (IBIOMED), University of León, León, Spain.
Pharmacy Service, Complejo Asistencial Universitario de León, León, Spain.
Int J Med Sci. 2017 Sep 4;14(11):1065-1071. doi: 10.7150/ijms.20245. eCollection 2017.
Abdominal radiotherapy (RT) causes harm to the mid gastrointestinal mucosa by release of pro-inflammatory cytokines and promotes autophagic changes in tumor cells. This study was aimed to measure the effect of glutamine administration on markers of inflammation and autophagy in cancer patients treated with RT. In this double-blind, randomized, controlled pilot trial 43 patients under abdominal RT diagnosed of pelvic or abdominal malignancies receiving glutamine (30 g/d) or placebo (casein, 30 g/d). Patient recruitment took place in the Complejo Asistencial Universitario of León (CAULE), Spain. Patient evaluation took place at three different time points during the study: before RT (pre-treatment), in the middle of the RT period (mid-treatment), and after finishing RT (post-treatment). Data were compared by analysis of variance and the Newmann Keuls test. Significance was accepted at p < 0.05. Abdominal RT increased whole blood mRNA levels of inflammatory and autophagic markers, but glutamine administration showed significantly lower expression of toll-like receptor 4 (TLR4), CD36, interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), and matrix metalloproteinase-9 (MMP-9). Moreover, glutamine reduced the expression of the transcription factors nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1). Glutamine also inhibited the autophagic response, with changes in expression of beclin-1, UV radiation resistance associated gene (UVRAG), autophagy-related protein-5 (Atg5), protein 1 light chain 3 (LC3), sequestosome 1 (p62/SQSTM1) and lysosome-associated membrane protein (LAMP)-1. Findings provide evidence that glutamine decreases the inflammatory response and abolishes the changes of the autophagy machinery in patients receiving abdominal RT. The protective effect of glutamine must continue being investigated to disclose further molecular pathways.
腹部放疗 (RT) 通过释放促炎细胞因子对中胃肠道黏膜造成损害，并促进肿瘤细胞发生自噬变化。本研究旨在测量给予谷氨酰胺对接受 RT 治疗的癌症患者炎症和自噬标志物的影响。
在这项双盲、随机、对照的初步试验中，43 名接受腹部 RT 治疗的盆腔或腹部恶性肿瘤患者被随机分为谷氨酰胺（30 g/d）或安慰剂（酪蛋白，30 g/d）组。患者招募在西班牙莱昂大学附属医院（CAULE）进行。患者评估在研究期间的三个不同时间点进行：在 RT 前（治疗前）、RT 期间中期（治疗中期）和 RT 结束后（治疗后）。通过方差分析和 Newmann Keuls 检验比较数据。接受 p < 0.05 的差异具有统计学意义。
腹部 RT 增加了全血中炎症和自噬标志物的 mRNA 水平，但谷氨酰胺给药显示 Toll 样受体 4 (TLR4)、CD36、白细胞介素 1β (IL-1β)、肿瘤坏死因子-α (TNF-α)、环氧化酶-2 (COX-2) 和基质金属蛋白酶-9 (MMP-9) 的表达明显较低。此外，谷氨酰胺降低了转录因子核因子 kappa B (NF-κB) 和激活蛋白 1 (AP-1) 的表达。谷氨酰胺还抑制了自噬反应，改变了 beclin-1、紫外线辐射抗性相关基因 (UVRAG)、自噬相关蛋白-5 (Atg5)、蛋白 1 轻链 3 (LC3)、自噬相关蛋白 12 (Atg12)、自噬相关蛋白 16L1 (Atg16L1) 的表达。
研究结果提供了证据表明，谷氨酰胺可降低接受腹部 RT 治疗的患者的炎症反应，并消除自噬机制的变化。必须继续研究谷氨酰胺的保护作用，以揭示进一步的分子途径。
