Experimental Study On Anti-Tumor Effects Of Tyroserleutide And Its Mechanisms By Activating Monocyte-Macrophages

Objective: To research the anti-tumor effects of the tripeptide tyroserleutide and advanced search for its possible anti-tumor mechanisms .Methods: The application of H22 H22 carrying mouse model for ascitic fluid type liver cancer was used to examine the effects of tyroserleutide on tumor-bearing mice.To apply human hepatocarcinoma BEL-7402 transplanted tumor in nude mice to use to examine the anti-tumor effects of tyroserleutide. To investigated the growth inhibition of tyroserleutide on human liver cancer BEL-7402 cell line by MTT colorimetric assay.To explore the activation effects of tyroserleutide on the M 4> functions of cytotoxicity against tumor cell lines (BEL-7402,B16-F10) in vitro and in vivo, phagocytosis of monocyte-macrophags system, and to detected the content of IL-1B TNF- a and NO produced by the M by employing ELISA method and enzyme reduction method.Results: Tyroserleutide can significantly increase the life span of H22 tumor-bearing mice by 50-70% in dosages of 20ug/kg/d-80ug/kg/d,specially the high dosage of 80ug/ml can significantly increase the life span by 69.24%; Tyroserleutide can inhibit the growth of transplanted hepatocellular tumor BEL-7402 in nude mice,the rate of tumor inhibition was25-50% in dosages of 40-320ug/ml ,the inhibition rate of 160ng/ml was 44.03%; Tyroserleutide could inhibit the growth of H22 and BEL-7402 tumor in a dose-dependent manner. Simultaneously, tumoricidal activity of tyroserleutide against BEL-7402 cell line in vitro was observed hinger when compared with the control group(P<0.05).The inhibition effect of 72hrs was higher than 24hrs,48hrs,96hrs.And specially the high dosage of 160ug/ml can significantly inhibit growth of tumor cell by 19.36%. Tyroserleutide can activated PEM and marked enhance cytotoxicity andphagocytosis functions in vitro and in vivo. The OD values of cytotoxicity were observed hinger when compared with the control group(P<0.05).The cytotoxicity of macrophages activated by tyroserleutide against BEL-7402 and B16-F10 was 35.58%,61.2% in vitro and21.39%,47.63% in vivo. The cytotoxicity rate of nude mice PEM was 32.86%,73.07% in vivo. Furthermore, tyroserleutide alone could stimulated the production of IL-1B TNF- a and NO by M . Tyroserleutide and LPS could synergistically activated M producing more cytotoxicity effectors. Conclusion: Tyroserleutide had inhibition functions against hepatoma carcinoma .Its possible mechanisms were related to the affect that Tyroserleutide could inhibit tumor cell directively and induce tumor cells apoptosis or death effectively. Tyroserleutide, as factors for activition of M ,can increase the cytotoxicity and phagocytosis function. Tyroserleutide will be potentially useful in tumor therapy and have more advantages in cancer treatment.