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ABSTRACT:Objective To investigate the effect and mechanism of Hedgehog signaling pathway on the invasion of breast cancer cells in vitro.Methods The SHH,SMO and Gli-1 expression levels of breast cancer cell line MDA-231 and normal mammary epithelial cell line MCF-10A were detected by Western blot at protein level and by Real-time RT-PCR at mRNA level.Next,shRNA vector was transfected into the MDA-2 3 1 cells with highly expressed SMO,and the stable transfected cells were selected by G4 1 8 .Western blot and Real-time RT-PCR were performed to observe the inhibitory effect of RNAi on SMO expression.MTT assay was used to assess the influence of SMO siRNA on cell proliferation.Transwell assay was applied to observe cell invasion ability.The expressions of Gli-1,Snail,MMP-9,E-cadherin and Vimentin protein were determined by Western blot.Results Compared with those of normal mammary epithelial cell line MCF-10A,the expressions of SHH,SMO and Gli-1 were significantly increased.The invasion of MDA-2 3 1 cells was inhibited significantly after SMO silencing.Additionally, the protein expressions of Gli-1 , Snail, MMP-9 and Vimentin were obviously inhibited, and E-cadherin was significantly increased.Conclusion Mutative activation of Hedgehog signaling pathway in breast cancer cells promotes cell invasion probably through induction of epithelial-mesenchymal transition of the tumor cells.
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Objective To determine the preventive effect of Celecoxib on postoperative adhesion formation and its mechanism. Methods We divided 80 SD rats into 5 groups: Groups A, B, C, H and S. Rats in Groups A, B, C and H received the operation of peritoneum rubbing to promote adhesion formation. Group S underwent sham operation. Rats in Group B were given Celecoxib of 40 mg/(kg·d), those in Group C were also given Celecoxib of 20mg/(kg·d), and those in Group H were given sodium hyaluronate (HA) during the operation. On the 8th and 15th postoperative day, half of the rats were sacrificed, the extent of adhesion formation was assessed and the adhesive peritoneum was subjected to immunohistochemistry with VEGF and CD_(34). Results The extent of postoperative adhesion differed significantly among the five groups (P<0.01). Groups B and C had significantly fewer adhesions than Groups H and A. VEGF was expressed most highly in Group A, followed by Groups H, C and B, and most weakly in Group S. CD34 was expressed most highly in Group A, followed by Groups H, C and B, and most weakly in Group S. Conclusion Celecoxib provides durable inhibition of intra-abdominal adhesions in a murine model compared with HA. The mechanism of preventing intra-abdominal adhesion via inhibiting COX-2 is possibly through down-regulated expression of VEGF and reduced microvascular density.
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Objective To study the corelation between the expression of COX-2 and postoperative adhesions and to determine the effect of COX-2 selective inhibitor,Celecoxib,on postoperative adhesion formation. Methods Fifty SD rats were randomly assigned to five groups each consisting of 10 rats,Study groups were as follows:(A)positive control group,(B)sodiumhyahronate group,(C)low dose Celecoxib group,(D)high dose Celecexib group,(E)negative control group,Five rats in each group were treated accordingly for consecutive 8 days and 15 days respectively and sacrificed,After treatment,intra-abdminal adhesions were scored using a standard method.The adhesions tissure and injured peritonaeum were subjected to Westem-blotting to detect the expression of COX-2. Results The level of postoperative adhesions and expression of COX-2 of sodiumhyahronate group、low dose Celecoxib group、high dose Celecoxib group were lower than that of positive control group(P<0.05),Sediumhyahronate treatment group was different formthe two Celecoxib treated groups(P<0.05).Conclusions Selective COX-2COX-2.mechanism,provides durable inhibition of intra-abdominal adhesions through an antiangiongenic COX-2 mechanism.
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Postoperative peritoneal adhesion represents a major complication of surgery. Recently, the angiogenesis which cyclooxygenase-2 enzyme induced was found to play an important role in the adhesion synthesis. This review summarized the relationship between COX-2 induced angiogenesis and peritoneal ad- hesion.