BCNU/PLGA microspheres:a promising strategy for the treatment of gliomas in mice简

Objective：To investigate the effects of BCNU/PLGA microspheres on tumor growth,apoptosis and chemotherapy resistance in a C57BL/6 mice orthotopic brain glioma model using GL261 cell line.Methods：BCNU/PLGA sustained-release microspheres were prepared by the water-in-oil-in-water emulsion technique.GL261 cells were intracranially injected into C57BL/6 mouse by using the stereotactic technology.A total of 60 tumor-bearing mice were randomly and equally divided into three groups：untreated control,PLGA treated,BCNU/PLGA treated.Magnetic resonance imaging （MRI） was taken to evaluate tumor volume.BCNU/PLGA sustained-release wafers were implanted in the treatment group two weeks after inoculation.Survival time and quality were observed.Specimens were harvested,and immunohistochemical staining was used to check the expression of Bax,Bcl-2,and O6-methylguanine-DNA methyltransferase （MGMT）.Statistical methods was used for analysis of relevant data.Results：BCNU/PLGA sustained-release wafers were fabricated and implanted successfully.There is statistical difference of survival time between the BCNU/PLGA treated group and control groups （P＜0.05）.MRIscan showed inhibitory effect of BCNU/PLGA on tumor growth.Compared to the group A and B,BCNU/PLGA decreased the expression of apoptosis related gene Bcl-2 （P＜0.05）,but did not elevate the expression level of Bax （P＞0.05）,with the ratio of Bax/Bcl-2 increased.For MGMT protein expression,no statistically significant change was found in treated group （P＞0.05）.Conclusions：Local implantation of BCNU/PLGA microspheres improved the survival quality and time of GL261 glioma-bearing mice significandy,inhibited the tumor proliferation,induced more cell apoptosis,and did not increase the chemotherapy resistance.