| Carcinoma of the uterine cervix is the second commonest female cancer worldwide. In order to understand carcinogenesis, development mechanism of cervical cancer, our previous study had selected the differential expression gene by cDNA gene chip and found many genes correlated strongly with development of early squamous cervical cancer. In these genes, the expression of macrophage migration inhibitory factor (MIF) in early squamous cervical cancer with lymph node metastased was higher than with no metastatic lymph node. We speculate MIF play an important role in cervical cancer devolpment.Purpose:To determine the correlation between the expression of macrophage migration inhibitory factor (MIF), CD74, PI3K, CyclinDl, Ki67 and devolpment of squamous cervical cancer and to provide a possible new clinical way for the theray of cervical cancer.Method:MIF, CD74, PI3K, CyclinDl, Ki67 protein expression was examined with immmunohistochemical analysis, Western blot analysis and enzyme linked immunosorbent assay (ELISA). Recombinant human MIF stimulate cervical cancer lines (C33A, Siha) to detect MIF-mediated cervical cancer cells proliferation by MTT analysis, expression of MIF, CD74, PI3K, CyclinDl, Ki67 protein by immmunohistochemical analysis, Western blot analysis. To further investigate the functions of MIF in cervical cancer, an inhibitor of MIF (ISO-1) stimulate cervical cancer lines (CaSki) to detect MIF-mediated cervical cancer cells proliferation by MTT analysis, expression of MIF, CD74, PI3K, CyclinDl, Ki67 protein by immmunohistochemical analysis, Western blot analysis.Result:MIF,CD74,PI3K,CyclinD1,Ki67 in human cervical carainoma cell line C33A, Siha, CaSki expression in both, and in highly metastatic cell lines CaSki expression,佛罗咯万æ¶çš„Siha in HPV16-positive cells, in the HPV-negative C33A cells and weakest in the low significant difference (P<0.05); Similarly, the three cervical cancer cell lines may secrete a certain amount of MIF protein in highly metastatic cell lines Caski secretion was significantly higher than in HPV16-positive Siha cells, in HPV-negative C33A cells and weakest in the low significant difference (P<0.05).Recombinant human MIF can stimulate cancer cell proliferation and the promotion of MIF, PI3K, cyclinD1, Ki67 expression in various cells.Specific inhibitor for MIF ISO-1 in human cervical cancer cell line Caski intestinal transfer significantly reduced proliferation activity, MIF, PI3K, cyclinDl, Ki67 protein expression was significantly decreased.Conclusion:MIF in various cancer cell lines to varying degrees, the expression intensity of high-risk type HPV infection in cervical cancer cells and metastic potential in the shows that MIF is involved in inflammation and tumor development, important cytokines. MIF can directly promote cancer cell proliferation, or by up-regulating the expression of cyclinD1, thereby affecting cell cycle progression, promotion of malignant proliferation of cancer cells. ISO-1 can directly inhibit MIF expression in cervical cancer cells and secretion, inhibit cancer cell proliferation, or reduced expression of cyclinDl reduce the cervical cancer cell proliferation.For This process may need the involvement of PI3K/Akt cell signaling pathway, but the exact mechanism needs further study. MIF in cervical cancer cell proliferation in mechanism of action will contribute to better understanding of the occurrence and development of cervical cancer, cervical cancer diagnosis to provide a theoretical basis for the personality of the treatment of cervical cancer to find a new way. |