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Experimental Study On The Treatment Of Proteasome Inhibitor MG-132 On Glioma

Posted on:2009-08-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:T H YuFull Text:PDF
GTID:1114360245963161Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective: To investigate the effect of porteasome inhibitor MG-132 on the glioma. Methods: In vitro and in vivo exprimental models was established by C6 glioma cell culture in vitro and planting C6 glioma intracranialy. Methods: MTT,HE staining,transmission electronic microscope,AO/EB staining with fluresence microscope,FCM,immunochemistry,in situ hybrid and MRI analyzed the effect of inhibiting proliferation and inducing apoptosis by proteasome inhibition of MG-132. Results: 1,In vitro experiment, MTT showed glioma proliferation inhibition was dependent on the doses of the MG-132 and suffering time; HE staining showed the volume of glioma cell decreased after MG-132 treatment and dispersing density also reduced, cytosol and nucleus condensed and presented apoptosis manifestation. AO/EB staining showed the cytosol became yellow or orange and nucleus became red. Transmission electronic microscope showed chrosome condenced. Immunochemistry showd Bcl-2 showd negtive staining; P53 showed posistive staining after treatment with MG-132. FCM showd the apoptosis rate peaked after 48h treatment with MG-132 at 20μmol/L. In the in vivo experiment, the volume of C6 glioma reduced significantly. The average volume of control group was 5.1±0.6mm and the experiment group was 3.2± 0.2mm (P<0.01). The immunochemistry showed the expression of P53 up- regulated and Bcl-2 down-regulated. In situ hybrid showed, C-myc mRNA reduced significantly and P16 mRNA upregulated significantly. TUNEL showed the apoptosis rate of tumor increased with the elongation of using MG-132. Conclusion:Proteasome inhibitor MG-132 inhibits the proliferation of glioma cells and induces them apoptosis.
Keywords/Search Tags:glioma, apoptosis, proteasome inhibitor
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