Effect Of Macrophage Migration Inhibitory Factor On Cell Proliferation And Angiogenesis In Human Colon Carcinoma

Objective: recently some investigate showed that macrophage migration inhibitory factor(MIF) have higher expression in more tumors and may be participated to angiogenesis,cell proliferative and immigration.but the specific mechanisms not clearly.this experiment to observe the Anti-MIF effect on cell proliferation and angiogenesis in human colon carcinoma and discussion the effective in tumor growth and development.Methods: The cell proliferative effect of Anti-MIF on human colon carcinoma HCT-116 cell line at different concentration and time(h)was measured by using MTT;The changes of HCT-116 cell cycle after treatment with different concentration Anti-MIF at 72 hour was determined by flow cytometry assay;The expression of vascular endothelial growth factor(VEGF) was examined by immunohistochemical stain and western-blot.Results: After HCT-116 cell were exposed to Anti-MIF (100,200,400 and 800μg/L)for different times .The 24h group cell inhibition rates were 1.02%, 3.09%, 8.62% and 15.28%;The 48h group cell inhibition rates were 2.16%, 6.83%, 18.24% and 38.20%;The 72h group were 5.09%, 12.92%, 33.91% and 53.56%. Anti-MIF displayed a strong growth effect in a dose and time-dependent manner against HCT-116 cells. Especially the 72h group ,all have statistical significance (p<0.05) to compared with negative group ;and significant difference(p<0.01)when compared with ento-group. The changes of HCT-116 cell cycle to Anti- MIF (100,200,400 and 800μg/L) for 72h,FCM analysis showed the G0/G1 phase ratio increased,S and G2/M phase ratio decreased;Especially the 800μg/L group , all have statistical significance(p<0.05)when G0/G1,S and G2/M stage compared with 0μg/L group. Anti-MIF have obviously inhibitory action to expresstion of VEGF on HCT -116 cells.The expression reduction to follow with Anti-MIF dos increasing;after exposure of the cells to Anti- MIF(100,200,400and800μg/L) for 72h, the expression of VEGF proteinum were(20567.48±1522.19, 7188.03±1011.59, 13920.21±1305.72, 13256.5±1266.09 and 11845.62±1071.20),all have statistical significance (p<0.05) . compared with negative group.Conclusion: Anti-MIF can active suppression cell proliferative by participates in the accommodation of cell growth cycle,to extend the cyclea and to hinder enter DNA synthesis period .Anti-MIF cause to degraded the expression of VEGF and MIF plays an important role in the pathogenesis of colon carcinoma by effect neovascularization of tumor with VEGF.