Effects of methionine enkephalin on immune enhancement by reducing myeloid derived suppressor cells and reprogramming liver metabolism in colon cancer mice

Ming XIANG,Ya-li TUO,Qi CHENG,Qian-qian XU,Hui CAO,Rong FU

(Department of Pharmacology,School of Pharmacy,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

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Effects of methionine enkephalin on immune enhancement by reducing myeloid derived suppressor cells and reprogramming liver metabolism in colon cancer mice

Ming XIANG,Ya-li TUO,Qi CHENG,Qian-qian XU,Hui CAO,Rong FU

(Department of Pharmacology,School of Pharmacy,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

OBJECTIVETo investigate enhanced immune function of methionine encephalin(MENK)and its anti-tumor mechanism in CT26 colon cancer mouse model.METHODS3×106CT26 cells were implanted subcutaneously in BALB/c mice.Four days after,MENK was peritoneally administrated at the concentration of 20 mg·kg-1for 14 d.The percentage of MDSCs in bone marrow,spleen,blood,tumor and liver were detected by flow cytometry.Non-esterified fatty acid(NEFA),triglycerides(TG)and total cholesterol(T-CHO)in liver homogenate were tested by a NEFA test kit,a TGtest kit and a T-CHO test kit respectively.qRT-PCR and Western blot were used to measure mRNA and protein levels of inflammation-,glycometabolsim-and lipometabolsim-associated indexes in liver.RESULTSMENK decreased percentages of MDSCs in bone marrow,spleen,blood and tumor in colon cancer mice.MENK-treated mice displayed elevated ratio of CD4+T and CD8+T cells in spleen as well as increased T and B lymphocytes proliferation.Meanwhile,MENK also ameliorated liver damage reflected by lower levels of GPT and GOT in serum and reduced risks of cancer-associated index including inflammation,high lipid and high glucose.Furthermore,MENK lowered down the levels of NEFA,TGand T-CHO in liver homogenate.MENK treatment decreased expression of p-STAT3,increased expression of p-AKT,IRS1 and Glut4 at protein level as well as reduced lipogenesis-associated genes and elevated glycolysis-associated genes in liver of tumor bearing mice.Also,abated expression of genes associated with MDSCs generation(M-CSF,GM-CSF,IL-6,IL-1β)and migration(S100A9,KC)was observed within shrunken subcutaneous tumor by MENK intervention.CONCLUSIONMENK has the ability to strength immune function against colon cancer by reducing MDSCs and improving liver metabolism.

methionine enkephalin;myeloid derived suppressor cells;liver metabolism

The project supported by National Natural Science Foundation of China(81673440 and 81473585)

Ming XIANG,Tel:00862783692745,E-mail:xiangming@mails.tjmu.edu.cn