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).MRI scan 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 significantly,inhibited the tumor proliferation,induced more cell apoptosis,and did not increase the chemotherapy resistance.
