The Anti-tumor Growth And Anti-angiogenesis Of Xanthain In Murine Glioma Dynamically Evaluated By MRI And DCE-MRI

Background: Glioma,the most common intracranial tumor,carries a high morbidity,recurrence and mortality,but the chemotherapy has been limited because of drug-resistance.Anti-angiogenesis therapy has been one of the important strategies in glioma treatment.Magnetic Resonance Imaging(MRI)is the first choice method for diagnosis,differential diagnosis,pathological gradation and prognosis gioma in clinical and scientific research.Xanthatin as a natural sesquiterpene lactone isolated from a native herb used in China called Xanthium strumarium L.was demonstrated to have an anti-tumor effect in several cell lines.Objective: The purpose is to investigate whether Xanthatin suppresses glioma growth in a cellular level,nude mice xenograft model and rat orthotopic implantation model.We also want to investigate whether the conventional MRI and the dynamic contrast enhanced MRI(DCE-MRI)can be used to dynamically monitor the anti-tumor growth and evaluate the anti-angiogenesis of Xanthatin,respectively.Methods: The cells experiment in xanthatin's anti-tumor effect was conducted first,the cell morphology was observed under microscope.Then the nude mice xenograft tumor model and rat orthotopic implantation model were established to observe the anti-tumor effects of Xanthatin in vivo.In rat orthotopic implanted tumor model,the conventional MRI and DCE-MRI scanning were used to dynamically monitor the anti-tumor effect and evaluate the anti-angiogenesis effect of Xanthatin,respectively.The anti-tumor effect of Xanthatin in vivo was confirmed by HE staining.VEGF expression in tumor tissue was detected by immunohistochemical method.Results: Xanthatin suppressed the proliferation of the C6 glioma cell in vitro dose dependently.Then we confirmed the results by building 30 C6 glioma tumor-bearing nude mouse.The size(604.55±107.82mm3 vs.2293.25±393.96mm3,P<0.01)and the weight(0.68±0.15 g vs.2.22±0.44 g,P< 0.01)of the tumor in the group treated with xanthatin at the dose of 0.4 mg/10 g was lower than the control group.In the assay of the rat orthotopic transplanted tumor(n=30,5 group),we ended up with the same result through MRI data.The body weight of rats after treatment with the TMZ(293.80±4.97 g vs.275.60±9.21 g,P < 0.05)and xanthatin at dose of 16mg/kg group(302.50±3.21 g vs.275.60±9.21 g,P < 0.05)was obviously larger than the control group and the size of the glioma in the TMZ group(42.54±11.18mm3 vs.85.19±14.76mm3,P < 0.01)and in xanthatin at dose of 16mg/kg group(22.57±8.64 mm3 vs.85.19±14.76 mm3,P < 0.001)was significantly smaller than the control group.The Ktrans value of the dynamic contrast-enhanced-MRI in xanthantin at dose of 16mg/kg group(0.045± 0.023min-1 vs.0.335±0.096min-1,P<0.05)was lower than the control group,which reflected that xanthatin influence angiogenesis in glioma.Another result that the expression of VEGF in tumor tissues in the xanthain high dose group was less than the control group demonstrated the result obtained through DCE-MRI.Conclusion: These data demonstrate the suppressive effects of xanthatin on C6 glioma via anti-angiogenesis.Meanwhile,this study also provides an evidence for the application of the conventional MRI and the quantitative parameters of DCE-MRI in dynamically evaluating the growth of intracranial tumor and anti-angiogenesis in the experimental and clinical research.