Radiotherapy Sensitization Of VPA-BSANPs On C6?U87glioma Cell Line

Object Glioma is the most common primary malignant brain tumor in adults.It is not only a poor prognosis,but also a serious threat to people's physical and mental health,affecting people's quality of life..Clinically,The conventional methods of treatment for glioma include surgery,chemotherapy,radiotherapy and so on Radiation therapy is an important adjunctive therapy for glioma,and its mechanism is to inhibit the proliferation of tumor cells by inducing DNA damage or producing free radicals.Because there are many factors that influence the effect of radiotherapy,the radiotherapy effect of glioma is not ideal,So it is very important to improve the therapeutic effect of glioma by adding sensitizer.Studies have shown that histone deacetylase(HDAC)inhibitors can enhance the sensitivity of tumor cells to radiotherapy,the mechanism is to induce tumor cell growth arrest and apoptosis.Sodium valproate(VPA)is one of the most common antiepileptic drugs,can be used for the prevention and treatment of epilepsy symptoms of patients with brain tumor.In recent years,sodium valproate(VPA)was found to be a very effective histone deacetylase inhibitor can increase the sensitivity of colon cancer cells toradiotherapy.In recent years,nanotechnology has become a hot spot in the field of tumor therapy.Because of its customization and multifunctional,nano materials play a more and more important role in tumor targeted therapy.Folic acid is a low molecular weight of the vitamin,at the desired nucleotide production of carbon transfer plays an important role in the unit,because of its high stability,low immunogenicity,unlimited availability,compatibility with organic solvent and water,with many molecular conjugation and the influence of carrier size is limited.We choose folic acid as a functional ligand.The folate receptor(FR)is a cell proliferative protein that is overexpressed in many types of cancer cells,including breast cancer,kidney cancer,head and neck cancer,lung cancer and colorectal cancer.Previous studies have shown that U87 is derived from glioblastoma,which is highly expressed in the pathological type,C6 cells belong to astrocytomas,and folic acid is moderately expressed in this type.So in this study we use folic acid as a nano material coated VPA composite(VPA-BSANPs),to observe the effect of sodium valproate(VPA)and VPA-BSANPs on C6 and U87 glioma cell lines in vitro radiosensitivity,provide powerful experimental basis for radiotherapy of glioma.Methods C6,U87 cells were treated with different concentrations of VPA and VPA-BSANPs,12h and 24h were used to detect the survival rate of cells by MTT method.C6,U87 glioma cells were treated with different concentration of VPA or VPA-BSANPs complex joint X-ray irradiation,detected cell survival fraction by clone formation assay?C6,U87 glioma cells were treated with different concentration of VPA,VPA-BSANPs complex role 12h,after different doses(0 Gy,4 Gy,8 Gy)of X-ray irradiation,Application of double staining flow cytometry to detect each cell apoptosis.Using western blotting method to detect the VPA,VPA-BSANPs complex role for the influence of radiation induced apoptosis protein expression.Result Without irradiation,the apoptosis of the VPA,VPA-BSANPs complex was not obvious both in C6 and U87 cells.The cell survival fraction of VPA-BSANP combined with radiotherapy group was significantly lower than that of VPA combined with radiotherapy group,and cell survival fraction dropped with the increase of irradiation dose.In C6 and U87 cells,VPA-BSANPs compound plus radiation group,the expression of Bax and P53 increased,while the expression of Bcl-2 decreased.The activation of Caspase3 fragments are only found in the VPA-BSANPs complex combined with radiotherapy group and VPA combined with radiation group,and the expression of VPA-BSANPs complex combined with radiation group was lower than that of VPA combined with radiotherapy group.The activation fragment alone radiation group and no caspase3.The active fragment of PARP was only found in the VPA-BSANPs complex combined with radiation groupConclusion VPA-BSANPs complex can increase the sensitivity of C6 and U87 glioma cell line in vitro by inducting the apoptosis of tumor cells induced from radiation.