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《Jiangsu Medical Journal》 2007-01
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Celastrol inhibits human glioma xenograft

HUANG Yulun,ZHOU Youxin,JIANG Hua,et al. Department of Neurosurgery,Affiliated First Hospital,Soochow University,Suzhou 215006,CHINA  
Objective To investigate the effects of celastrol on the growth of human malignant glioma cell line SHG-44 in vivo and study the mechanism that celastrol inhibits the growth of a human malignant glioma cell line SHG-44 in vivo.Methods Animal models were established on BALB/c nude mice with subcutaneously transplanted neoplasma of SHG-44 glioma.The nude mice bearing with SHG44 glioma were devided randomly into five groups, which were treated without drugs or with different doses of celastrol(4mg/kg,2mg/kg and 1mg/kg) or with cisplatin(2mg/kg).The dimension of xenografts was measured and the living state of nude mice with SHG-44 glioma was observed.The protein expression of microvessel density(MVD),bFGF,cyclin D1,PCNA in each paraffin imbedded xenograft of nude mice bearing with SHG-44 glioma were detected by immunohistochemistry staining.Results Celastrol at both 4mg/kg and 2mg/kg inhibited the growth of xenografts in nude mice with SHG44 blioma(P0.05),and the tumor volume was reduced by 35% and 26.9% in both of celastrol-treated groups respectively compared with that in the dissolvent control.Meanwhile the control group highly expressed bFGF at the level of protein,coupling with increase of MVD.Compared with the dissolvent control group,two groups of celastrol 4mg/kg and 2mg/kg showed lower expression of them(P0.05) and more decrease in MVD(P0.05).The protein expression of PCNA and cyclin D1 in two groups of celastrol 4mg/kg and 2mg/kg was dose dependently lower than that in control group(P0.05).Conclusion Celastrol can inhibit the growth of a human malignant glioma cell line SHG-44 in vivo significantly and dose-dependently.Celastrol can significantly suppress the expression of bFGF, PCNA and cyclin D1 at the level of protein.The mechanism of supressing glioma may be a down-regulation of protein expression of bFGF resucting in the inhibition of angiogenesis.In virtue of regulating cell-cycle,the down-regulation of PCNA and cyclin D1 protein expression may suppress the proliferation of neoplasma.
【Fund】: 江苏省135重点学科基金资助(苏卫科教200319号)
【CateGory Index】: R739.4
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