Tian Yun, Wang Keming, Fan Yingrui, Wang Yan, Sun Liqun, Wang Li, Wang Jirong, Wang Zhaoxia, Li Juan, Ye Ying, Ji Guozhong
Department of Oncology, the Second Affiliated Hospital of Nanjing Medical University, No. 121 Jiangjiayuan Road, Nanjing 210011, China.
Department of Pathology, the Second Affiliated Hospital of Nanjing Medical University, No. 121 Jiangjiayuan Road, Nanjing 210011, China.
Nutrients. 2016 May 2;8(5):261. doi: 10.3390/nu8050261.
Glutamine plays a protective role in colitis and colitis-associated colorectal cancer (CAC); however, the protective mechanisms are largely unknown to date. DEP domain-containing mTOR-interacting protein (DEPTOR)/mammalian Target of Rapamycin (mTOR) signaling plays an important role in carcinogenesis. The present study investigated the potential molecular mechanisms for the protective effect of glutamine in a murine model of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC. The effects of glutamine on DEPTOR/mTOR signaling and protein light chain 3 (LC3) were evaluated. Administration of glutamine was associated with attenuated development of CAC. Increased expression of DEPTOR and decreased expressions of factors of mTOR signaling, including phospho-mTOR, phospho-STAT3, phospho-Akt, and phospho-S6, were observed in AOM/DSS mice administered glutamine. Furthermore, oral glutamine was associated with increased LC3-II expression in AOM/DSS mice. The present study indicates that regulation of DEPTOR/mTOR signaling may be an important mechanism for glutamine in prevention against the development of CAC. In addition, the chemopreventive effect of dietary glutamine on CAC is, at least in part, associated with the induction of autophagy.
谷氨酰胺在结肠炎及结肠炎相关结直肠癌(CAC)中发挥着保护作用;然而,其保护机制至今仍 largely 未知。含DEP 结构域的 mTOR 相互作用蛋白(DEPTOR)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路在肿瘤发生中起重要作用。本研究在氧化偶氮甲烷(AOM)/葡聚糖硫酸钠(DSS)诱导的 CAC 小鼠模型中探究了谷氨酰胺发挥保护作用的潜在分子机制。评估了谷氨酰胺对 DEPTOR/mTOR 信号通路及微管相关蛋白 1 轻链 3(LC3)的影响。给予谷氨酰胺与 CAC 的发展减缓相关。在给予谷氨酰胺的 AOM/DSS 小鼠中,观察到 DEPTOR 表达增加,以及 mTOR 信号通路相关因子的表达降低,包括磷酸化 mTOR、磷酸化信号转导子和转录激活子 3(STAT3)、磷酸化蛋白激酶 B(Akt)和磷酸化核糖体蛋白 S6。此外,口服谷氨酰胺与 AOM/DSS 小鼠中 LC3-II 表达增加相关。本研究表明,调控 DEPTOR/mTOR 信号通路可能是谷氨酰胺预防 CAC 发展的重要机制。此外,膳食谷氨酰胺对 CAC 的化学预防作用至少部分与自噬的诱导有关。