Macrophage Migration Inhibitory Factor Regulating Apoptosis Of Cerical Cancer Cells Via PI3K Pathway

Purpose: To investigate the effects of MIF on apoptosis of hunman cerical cancer cells andexpression of PI3K,p53and Bcl-2 in them,and further determine whether the effects are relatedto the PI3K/Akt signal transduction pathway.Our research is to study the possible mechanism ofapoptosis by MIF-mediated,provide a possible effective new clinical way for the therapy ofcervical cancer.Methods: Cervical cancer CaSki and Siha cells were cultured and then treated with 100μg/Lrecombinant human MIF (rhMIF) with and without a PI3K inhibitor , LY294002 (25μmol/L).MTT assay and Flow Cytometry was used to detect the proliferation and apoptosis of cervicalcancer CaSki and Siha cells ; Western Blotting detection and immunocytochemistry was used todetect the protein expression of PI3K , pAkt , p53 and Bcl-2 .Results: Western blotting and immunocytochemistry showed that the protain express of MIFin the CaSki and Siha cells and more higer in the CaSki cells.Western blotting andimmunocytochemistry showed that rhMIF significantly stimulated the proliferation of cervicalcancer CaSki and Siha cells and protein expression of PI3K , pAkt , p53 and Bcl-2 . The MTTassay and flow cytometry showed that treatment with rhMIF significantly increased theproliferation of cervical cancer CaSki and Siha cells in a dose- and time-dependent mannercompared with the controls; Western blotting and immunocytochemistry showed that aftertreatment with 100μg/L rhMIF for 24h, the expression of PI3K , pAkt ,p53 and Bcl -2 proteinwas significantly up-regulated at protein levels. However, the cervical cancer CaSki and Sihacells were treated with LY294002 without rhMIF treatment can down-rugulated the expressionof PI3K, pAkt , p53 and Bcl-2 proteins and promoted the proliferation. The cervical cancerCaSki and Siha cells were treated with rhMIF and LY294002 inhibit the apoptosis .Conclusion: MIF increases the proliferation and inhibits apoptosis of cervical cancer CaSki andSiha cells, induces the expression of PI3K, pAkt , p53 and Bcl-2 at the protain level. ExogenousrhMIF can promote the protein expression of p53 and Bcl-2 to inhibit the apoptosis of cericalcancer. The process of MIF enhances the proliferation and up-regulated expression of PI3K , p53and Bcl-2 proteins may need the activement of PI3K/Akt cell signaling pathways .