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The Study Of Antigliomatin Inhibitory Effects On C6 Brain Glioma In Rats

Posted on:2005-07-02Degree:MasterType:Thesis
Country:ChinaCandidate:H Y JiangFull Text:PDF
GTID:2144360125950552Subject:Neurology
Abstract/Summary:PDF Full Text Request
Primary brain tumors (gliomas) are the most common malignant tumors in central nervous system They constitute a heterogeneous group of tumors associated with significant morbidity and mortality.Gliomas are characterized by a high invasive potential and display a wide diversity of histological features. They derived from glial support cells in the brain and the vast majority are thought to be of astrocytic origin. Even low-grade gliomas infiltrate the entire brain ,a feature that precludes their successful therapy. Therefore it is very difficult to eradicate by operation and not sensitive to drugs of accessory treatment methods to target cells. It has a significance to seek for a kind of drugs that has high effective and low side-effect. Molecular mechanisms of brain tumor invasion are complex.It has been reported that a large voltage-dependent chloride (Cl-) currents selectively expressed by human glioma cells in vitro and in situ.Invading glioma cells undergo dramatic shape and cell volume changes allowing them to make their way through the narrow extracellular spaces .Currents are sensitive to several Cl- channel blockers,including chlorotoxin(Ctx),tetraethylammonium(TEA),and tamoxifen. Chlorotoxin is a scorpion toxin that specific-ally binds to the surface of glioma cells and impairs their ability to invade.Accordingly, It is a new drug to inhibit glioma cell growth and has tremendous application foreground to treat glioma.Objective : To study the inhibiting effect on the growth of rat brain C6 glioma and proliferated activity of the rat glioma model before and after chlorotoxin treatment.Methods : C6 glioma cells were seeded with high-flow microinfusion into right caudate nucleus of all rats with sterotactic technique . After raising for 7 days, rat brain glioma models ,that were testified by methods of pathology and GFAP immunohistochemistry,were builted. The rats were randomly assigned to 5 groups, In the four treatment groups ,they were given different concentration chlorotoxin for 7 times at abdominal cavity from the 7th days after cell inoculation. The control group received only 10ul 0.9% NaCl for 7 times .The size of glioma were measured, by which we calculate inhibitory rate .Proliferation and morphological change of glioma cells were detected by HE staining method, electron-microscopic observation and the technique of SABC immunohistochemistry.Results: The rats in treatment groups were better,while rats in control group were bad . Compared with the control group,the tumor size of rats in the treatments was decreased . Tumor volumes were measured , 32 ug/kg of chlorotoxin has obviously inhibiting effect on C6 glioma cells, inhibiting rate was 38.3%; inhibiting rate of 64 ug/kg reached 54.61%. The positive cells number of PCNA the treatment group is significantly less than the control group,and continued to decrease with the following concentration increasing . So we concluded that Antigliomatin had apparent inhibiting effects on C6 glioma cell and induced apoptosis to C6 cells.Conclusions: It suggests that Antigliomatin could inhibit the growth of rats brain glioma cells ,its pathogenesis can be related with inducing cells apoptosis and inhibiting cell proliferation ,which established important theoretical basis for its clinical application.
Keywords/Search Tags:Glioma, C6 cell, Antigliomatin, chlorotoxin, PCNA
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