Celastrol On The Inhibition Of A Human Malignant Glioma Cell Line SHG-44 In Vivo

First partObjective: The aim of this study is to investigate the effects of Celastrol on the growth of a human malignant glioma cell line SHG-44 in vivo.Methods: Animal models were constructed on BALB/c nude mice with subcutaneously transplanted neoplasma of SHG-44 glioma. The nude mice bearing with SHG44 glioma were devided into five groups by random selection, which were treated without drugs or with different doses of Celastrol(4mg/kg, 2 mg/kg and 1mg/kg, ip twice weekly for four weeks)or with Cisplatin(2 mg/kg, ip twice weekly for four weeks). The dimension of xenografts were measured and the living state of nude mice with SHG-44 glioma were observed.Results: Celastrol at both 4mg/kg and 2mg/kg can inhibit the growth of xenografts in nude mice with SHG44 glioma (P<0.05), and the tumor volume was reduced by 35% and 26.9% in both of Celastrol-treated groups respectively compared with the control.Conclusion: Celastrol can inhibit the growth of a human malignant glioma cell line SHG-44 in vivo significantly and dosage-dependently.Second partObjective: To study the mechanism that Celastrol inhibits the growth of a human malignant glioma cell line SHG-44 in vivo.Methods: The protein expression of MVD,bFGF,VEGF,VEGFR1, VEGFR2,PCNA and Cyclin Dl in each paraffin imbedded xenograft of nude mice bearing with SHG-44 glioma were detected by immunohistochemistry staining.Results: (1) Concerning the protein expression level of VEGF among five groups, there is no significant deviation (P>0.05). Meanwhile the control group can highly express bFGF> VEGFR 1 and VEGFR2 at the level of protein, coupling with increase of MVD. Compared with the control group, two groups of Celastrol at 4mg/kg and 2mg/kg show lower expression level of them (PO.05) and more decreasing MVD (PO.05). (2)The protein expression of PCNA and Cyclin Dl in two groups of Celastrol at 4mg/kg and 2mg/kg is lower than that of control group (P<0.05), which is related to the dose of Celastrol.Conclusion: Celastrol can significantly suppress the expression of bFGF> VEGFR 1 > VEGFR2^ PCNA and Cyclin Dl in the lever of protein, but there is no effect on the downregulation of VEGF. Therefore, the capital mechanism of repressing glioma may be: (1) down-regulation of VEGFR protein expression depresses biological effect of VEGF on angiogenesis in glioma and lower protein expression of bFGF may contribute to the inhibition of angiogenesis. (2) In virtue of regulating cell-cycle, the down-regulation of PCNA and Cyclin Dl protein expression may suppress the proliferation of neoplasma.