Yun Tian, Yingrui Fan, Li Wang, Keming Wang

Department of Oncology, the Second Affiliated Hospital of Nanjing Medical University

Objective:Glutamine shows a protective role in colitis and colitis-associated colorectal cancer (CAC), however, the protection mechanisms are largely unknown so far. DEP domain-containing mTOR-interacting protein (DEPTOR)/mammalian Target of Rapamycin (mTOR) signaling plays an important role in carcinogenesis. The present study investigated a molecular mechanism for the protective effect of glutamine in murine model of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC. Method: The DSS/AOM model of CAC was employed in this study according to our experimental treatment protocol reported previously. The effects of glutamine of DEPTOR/mTOR signaling and protein light chain 3 (LC3) were evaluated by pathological examination, Western blot analysis and immunochemical examination. Result: Administration of glutamine was associated with attenuated development of CAC (Table1). Increased expression of DEPTOR (Figure1, 2) and decreased expressions of factors of mTOR signaling including phosphor-mTOR, phosphor-STAT3, phosphor-Akt, and phosphor-S6 were observed in AOM/DSS mice receiving glutamine (Figure3). In addition, oral glutamine was associated with increased expression of LC3-II in AOM/DSS mice (Figure4). Conclusion: The present study indicates that regulation of the DEPTOR/mTOR signaling may be an important mechanism for glutamine in prevention against development of CAC. In addition, the chemopreventive effect of dietary glutamine on CAC is, at least in part, associated with induction of autophagy.

Key Words: Colitis Associated Colorectal Cancer Glutamine DEP