The Studies To Anti-tumor Effect And Its Mechanisms Of Celastrol On Human Colon Cancer Cell Line HCT-116

Partâ… Studies to anti-tumor effect and mechanism of celastrol on inhibition growth of human colon cancer cell HCT-116Objective:To investigate the effect and the mechanism of celastrol on inhibiting growth of human colon cancer HCT-116.Methods:MTT assay was used to calculate the effect of cell growth inhibition,cell cycle and apoptosis rate was analyzed by flow cytometry(FCM),election microscope was used to observe the morphologic change.The proteasome activity of HCT-116 cells was measured by detecting the fluorescence unites given out by substrates,and the protein expression of P27,Bax and P53 was evaluated by Western blot.Results:Celastrol inhibited HCT-116 cell growth significantly in dose and time dependent manner(P＜0.05).Flow cytometry display that celastrol can reduce HCT-116 cell apoptosis and induce G₁ arrest.After being treated with celastrol at the concentration of 7.0umol/L 24 hours,cellular nucleus became condensed,cytoplasm obviously cavitating,heterochromatin agglutinating,showing typical apoptosis changes in morphology.The cells were cultured with celastrol at 0.875-7.0umol/L.Sixteen hours later,Significantly inhibited proteasomal activities(P＜0.05)and the accumulation of P27,Bax and P53 could be observed in HCT-116 cells in a dose-dependent manner.Conclusion:Celastrol can inhibit proliferation of HCT-116 cell and arrest cell cycle. Celastrol can significantly inhibit the proteasomal activity and lead to an accumulation of P27,Bax and P53 protein in HCT-116 cells,which might be related to its anti-tumor effect. Partâ…¡The study of celastrol enhanced cytotoxicity of chemotherapy on human colon cancer cell line HCT-116Objectives:To study the combination effect and anti-tumor mechanism of celastrol and 5-Fu on human colon cancer cell lines.Methods:MTT assay was used to analyze the effete of celastrol and 5-Fu alone or in combination on the growth of HCT-116 cells.Flow eytometry was used to observe apoptosis.The expression of IκB was analyzed by Western blot.Results:Comparing with celastrol and 5-Fu alone,the inhibitory effect of celastrol combined with 5-Fu was increased(P＜0.05),the cell apoptosis rate was significantly increased(P＜0.05).Western blot showed that the transcription factor IκB was degraded by dealed with 5-Fu,However celastrol can inhibit the degradation of the transcription factor IκB.Conclusion:Celastrol could increase the cytotoxicity effect of 5-Fu on colon cancer cell line HCT-116,These effects may be associated with which decreased the degradation of the transcription factor IκB and suppress NF-κB activation.