| Macrophage migration Inhibitory Factor (MIF)is a multi-function of cytokines, which is secreted by the pituitary gland mesophyll, T lymphocytes and monocyte/Macrophage .MIF has a variety of biological function:(1) MIF's main function is to activate T lymphocytes and to stimulate B lymphocytes producing antibody in order to cause inflammation and stimulate tumor occurrence, development.(2) MIF is the most important medium of inflammation. When tissue injury and infection, LPS orα-TNF can induce MIF to release and to participate in tissue damage repairing;(3) MIF has neuroendocrine function, as a negative feedback regulating of pituitary hormone and glucocorticoids;(4) MIF has a variety of enzyme activity, such as dopamine pigment isomerase, hydroxyl benzene pyruvate isomerase and protein– mercaptoacetic redox enzyme. In recent years, MIF in the role of cancer occurrence, development ,invasion and metastasis was concerned. Its possible mechanism are that MIF up-regulation VEGF, TNF - beta and PDGF expression in order to promote the growth of blood vessels, tumor invasion and metastasis[7].MIF acts on cell signal transduction pathways of PKC, MAPK, ERK1/2, c-jun, Jab, CSNS and P27 in order to participate in cell proliferation; MIF inhibits P53 dependence cell apoptosis to cause cell apoptosis decreasing; MIF inhibits the role of NK cells which can kill tumor cells. MIF also can promote cancer genes expressing such as the expression of N-myc,C-fas.RNA interference is a kind of high efficient and specific gene silencing means. RNA interference is that dsRNA is imported into cells to cause special genes mRNA degradation.Small interfering RNA is the effector molecule of RNAi , which is complementation fixation with the purpose gene to induce whose mRNA not to translate protein.MIFsiRNA is chemical synthesis which can be complementation fixation with MIFmRNA to cause MIFmRNA to decompose and not to translate the protein.This study aims to analysis the influence on tumor growth and the quality of tumor-burdened mice by injection with MIFsiRNA, and discuss the possible mechanism.Methods:Employing the method of rthotopic transplantation that fresh tumor masses were planted into the hernial sac of cecum by operation, we established mouse model of colorectal cancer. Thirty mice after modeling were divided into three groups randomly and interfered with DEPC water,MIFsiRNA(0.15nmol/g) and non-specific siRNA(0.15nmol/g) twice a week by intratumoral injection. The drinking amount,feeding amount and body weight was measured every day, and tumor volume was measured once a week.Four weeks later,the mice were killed and the tumors were measured. ELISA was used to detect the expression of MIF and VEGF in serum. Immunohistochemistry was used to detect the expression of MIF in tumor tissues.Spectrophotometric detection was used to detect Caspase-3 Protein.TUNEL was used to detect apoptotic cell number.Results:MIF expression in serum in MIFsiRNA group mice decreased than the other two group〔s(22±6)ng/ml vs(32±8)ng/ml and (33±8)ng/ml,P<0.01〕,VEGF expression in serum decreased than the other two groups〔(1.367±0.078)ng/ml vs(1.792±0.145)ng/ml and (1.892±0.144)ng/ml,P<0.01〕; MIF expression in tissues was less than the other two group〔s(85±20)/500个vs (423±23)/500个and (442±31)/500个,P<0.01〕;Tumor volume was less than the other two groups after 24-31d of modeling (P<0.01); The tumor weight was significantly lighter than the other two groups〔(1.93±0.21)g vs (4.40±0.30)g and (5.25±0.44)g, P<0.01〕;After 15～21d of modeling,drinking amount was more than the other two groups(P<0.01);After 8～14d of modeling,feeding amount was more than the other two groups(P<0.01);The weight change of three groups mice had no statistical significance(P>0.05); Caspase-3 protein in tissues was higher than the other two groups〔(0.74±0.06)μg vs (0.57±0.08)μg and (0.56±0.02)μg,P<0.01〕;The number of apoptosis cells in tissues was higher than the other two groups〔(12±2)?100个vs 0 and 0,P<0.01〕.Conclusions:Knockdowning MIF gene expression can inhibit the growth of colorectal cancer xenografts and improve the life quality of tumor-bearing mice. The possible mechanism may be that MIFsiRNA activates Caspase-3 to promote cell apoptosis,and down regulates VEGF expression to inhibit tumor angiogenesis.
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