Structural modification and anti--tumor activity change of recombinant human endostatin
2005
Endostatin is an endogenous inhibitor of angiogenesis and tumor growth.GRIRGAD sequence was changed into RGDRGD by the method of site\|directed mutagenesis to raise its anti\|tumor activity.In nude mice,the tumor inhibition rate of wild\|type and mutant\|type endostatin were 40 66% and 51 05%, respectively.Anti\|tumor activity of mutant\|type endostatin increased by about 11% compared with that of wild\|type one.By histological study,the mutant\|type endostatin group had less angiogenesis and more necrosis areas than mutant\|type endostatin one.Immunohistochemical observation also showed that the mice treated with mutant\|type endostatin had a lower expression of MVD( P 0 05),VEGF( P 0 05) and PCNA( P 0 05).The MTT assay showed that the mutant\|type endostatin had a lower dose of IC 50 (27 μg/ml) than the wild\|type one ( IC 50 =185 μg/ml)and the anti\|tumor activity of the former was 6 times than that of the latter.Cellular migration assay showed that tumor cell migration was inhibited by both mutant\|type and wild\|type endostatin,with the inhibition rate 89 94% and 68 95%,respectively.The results suggest that in addition to inhibiting angiogenesis,endostatin can also inhibit proliferation and migration of tumor cell.The anti\|tumor activity of mutant\|type endostatin is raised with its RGDRGD sequence binding with integrin.
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