Inhibitory Mechanism Of L-MTP-PE Rat Peritoneal Macrophages On UMR106 Osteosarcoma Cells

The past 25 years have witnessed dramatic advances in clinical treatment of osteosarcoma. With the developments of limb-salvage surgery, adjuvant chemotherapy, radiotherapy and immunotherapy, The 5 years survival rate of osteosarcoma patients has increased significantly from 20% in 60' to 60%-75% today, But metastasis remains survival limiting factor.It is the major pathway of immunotherapy to augment the host immunoresistance against tumor and to kill the l%-2% remains of tumor cells after surgery and chemotherapy. Macrophage play important role in tumor immunity, which can be attributed to its augmenting effect on antigen presenting and nonspecific tumoricidal potentiation. Muramyl dipeptide(MDP) and its derivatives(MDPs) were found that they can activate the macrophage function specially and sufficiently, which makes it possible for MDP and MDPs to be effective antitumor drugs.In this research, Tuluylene red pinocytic test, indirect MTT assay, and nitrate reduction test were used to determine the non-specific anti-osteosarcoma function of SD rats peritoneal macrophages received L-MTP-PE in vitro. While ultrastructure observation, immuno-fluorescence flow cytometry, mixed lymphocyte reaction (MLR) and cytotoxicity T lymphocyte activity detection were used to evaluate antigen presenting activity of macrophages. SD rats with osteosarcoma were employed as the animal models to investigate the inhibitory effect of L-MTP-PE on tumor in vivo.Results and conclusions L-MTP-PE could significantly enhance the phagocytic function, stimulatethe level of cytokine TNF and NO secreted by macrophages, which was correlated to macrophages cytotoxic activity against UMR106 osteosarcoma. L-MTP-PE increased the number of cell surface microvilli and cell organelles of macrophages; brought on the high expression of MHC- II molecules on macrophages, which could promote the macrophages to deal with and present the tumor antigen to T lymphocyte, activating the specific CTL cellular immune responses more effectively. The proliferation of UMR106 osteosarcoma cells granted in SD rats subcutaneously administrated with L-MTP-PE was inhibited dosedependently, Macrophages activated by L-MTP-PE might play important role in the course of antitumor immunity.The research initially explored the pathway and mechanism of L-MTP-PE induced antitumor effect effect of macrophages from SD rats, provided initial evidence for further research of experiment and clinical application.