Department of Oncology, University of Alberta, Edmonton, Canada; Nutrition Laboratory EA 4466, Paris Descartes University, Paris, France; Univ. Grenoble Alpes, Inserm U1055, LBFA, Grenoble, France.
Nutrition Laboratory EA 4466, Paris Descartes University, Paris, France; Univ. Grenoble Alpes, Inserm U1055, LBFA, Grenoble, France.
Clin Nutr. 2021 Jul;40(7):4560-4568. doi: 10.1016/j.clnu.2021.05.035. Epub 2021 Jun 9.
During cancer therapy many patients experience significant malnutrition, leading to decreased tolerance to chemotherapy and decreased survival. Dietary citrulline supplementation improves nutritional status in situations such as short bowel syndrome and aging, and is of potential interest in oncology. However, a mandatory prerequisite is to test this amino acid for interaction with tumor growth and chemotherapy response. Dietary citrulline (Cit; 2%), or an isonitrogenous mix of non-essential amino acids (control), was given to Ward colon tumor-bearing rats the day before chemotherapy initiation. Chemotherapy included 2 cycles, one week apart, each consisting of one injection of CPT-11 (50 mg/kg) and of 5-fluorouracil (50 mg/kg) the day after. Body weight, food intake and tumor volume were measured daily. The day after the last injection, rats were killed, muscles (EDL, gastrocnemius), intestinal mucosa, tumor, spleen and liver were weighed. Muscle and intestinal mucosa protein content were measured. Phosphorylated 4E-BP1 was measured in muscle and tumor as a surrogate for biosynthetic activation. FRAPS (Ferric Reducing Ability of Plasma) and thiols in plasma, muscle and tumor were evaluated and plasma amino acids and haptoglobin were measured. Numerous parameters did not differ by diet overall: a) response of tumor mass to treatment, b) tumor antioxidants and phosphorylated 4E-BP1 levels, c) relative body weight and relative food intake, d) weight of EDL, gastrocnemius, intestinal mucosa, spleen and liver and e) plasma haptoglobin concentrations. Moreover, plasma citrulline concentration was not correlated to relative body weight, only cumulated food intake and plasma haptoglobin concentrations were correlated to relative body weight. Citrulline does not alter the tumor response to CPT-11/5FU based therapy but, has no effect on nutritional status, which could be due to the anorexia and the low amount of citrulline and protein ingested.
在癌症治疗过程中，许多患者会经历严重的营养不良，导致对化疗的耐受性降低和生存率降低。膳食瓜氨酸补充可改善短肠综合征和衰老等情况下的营养状况，并且在肿瘤学中具有潜在的研究价值。然而，强制性的前提是要测试这种氨基酸与肿瘤生长和化疗反应的相互作用。在化疗开始前一天，给 Ward 结肠荷瘤大鼠喂食膳食瓜氨酸（Cit；2%）或等氮非必需氨基酸混合物（对照）。化疗包括 2 个周期，间隔 1 周，每个周期由 CPT-11（50mg/kg）和 5-氟尿嘧啶（50mg/kg）的 1 次注射组成，在第 2 天进行。每天测量体重、食物摄入量和肿瘤体积。最后一次注射后的第 2 天，处死大鼠，称重肌肉（EDL、比目鱼肌）、肠黏膜、肿瘤、脾脏和肝脏，测量肌肉和肠黏膜的蛋白含量。测量肌肉和肿瘤中磷酸化 4E-BP1 作为生物合成激活的替代物。评估血浆、肌肉和肿瘤中的 FRAPS（血浆还原能力）和巯基，测量血浆氨基酸和触珠蛋白。总的来说，饮食对许多参数没有影响：a）肿瘤质量对治疗的反应，b）肿瘤抗氧化剂和磷酸化 4E-BP1 水平，c）相对体重和相对食物摄入量，d）EDL、比目鱼肌、肠黏膜、脾脏和肝脏的重量，e）血浆触珠蛋白浓度。此外，血浆瓜氨酸浓度与相对体重无关，仅累积食物摄入量和血浆触珠蛋白浓度与相对体重相关。瓜氨酸不会改变 CPT-11/5FU 基础治疗的肿瘤反应，但对营养状况没有影响，这可能是由于厌食和摄入的瓜氨酸和蛋白质数量较少所致。
