Fahr M J, Kornbluth J, Blossom S, Schaeffer R, Klimberg V S
Department of Surgery, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
JPEN J Parenter Enteral Nutr. 1994 Nov-Dec;18(6):471-6. doi: 10.1177/0148607194018006471.
It is known that tumor progression is associated with a depletion in host glutamine (Gln) stores and a depression of natural killer (NK) cell activity. After demonstrating an in vitro dependence of NK cell activity on Gln and glutathione concentration, this study evaluated the effects of oral Gln on Gln and glutathione metabolism, NK cell activity, and tumor growth in the tumor-bearing rat.
Two days before tumor implantation, rats (n = 32) were randomized to receive Gln (1 g/kg/d) or an isonitrogenous amount of glycine by gavage and pair-fed food. On day 21 after tumor implantation, rats were killed, and tumors were measured and processed for glutaminase activity, glutathione content, and tumor morphometrics. Splenic lymphocytes were assayed for NK cell activity via a chromium (51Cr) release assay using YAC (NK-cell-sensitive mouse tumor cell line) target cells. Blood Gln and glutathione were measured. A second set of rats (n = 16) were treated similarly except that ketamine was given twice weekly to suppress NK cell activity.
During the 3-week study period, tumor growth was decreased by 40% in the Gln group. This decrease in growth was associated with a 30% increase in NK cell activity. Administration of ketamine to rats completely reversed the higher NK cell activity and decreased the tumor growth seen in the Gln-treated group.
These data indicate that oral Gln supplementation, through support of host Gln stores and glutathione production, may decrease tumor growth by enhancing NK cell activity.
已知肿瘤进展与宿主谷氨酰胺（Gln）储备的消耗以及自然杀伤（NK）细胞活性的降低有关。在证明NK细胞活性在体外依赖于Gln和谷胱甘肽浓度后，本研究评估了口服Gln对荷瘤大鼠体内Gln和谷胱甘肽代谢、NK细胞活性及肿瘤生长的影响。
在肿瘤植入前两天，将大鼠（n = 32）随机分为两组，分别通过灌胃给予Gln（1 g/kg/d）或等氮量的甘氨酸，并给予配对饲料。肿瘤植入后第21天，处死大鼠，测量肿瘤大小，并对肿瘤进行谷氨酰胺酶活性、谷胱甘肽含量及肿瘤形态学测量。通过使用YAC（对NK细胞敏感的小鼠肿瘤细胞系）靶细胞的铬（51Cr）释放试验检测脾淋巴细胞的NK细胞活性。检测血液中的Gln和谷胱甘肽水平。另一组大鼠（n = 16）接受类似处理，但每周两次给予氯胺酮以抑制NK细胞活性。
在为期3周的研究期间，Gln组肿瘤生长减少了40%。生长的减少与NK细胞活性增加30%相关。给大鼠注射氯胺酮完全逆转了Gln处理组中较高的NK细胞活性，并降低了肿瘤生长。
这些数据表明，口服补充Gln，通过支持宿主Gln储备和谷胱甘肽生成，可能通过增强NK细胞活性来减少肿瘤生长。
