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Published on: December 15, 2010
BCNU/PLGA microspheres: a promising strategy for the treatment of gliomas in mice
Tongming Zhu1, Yiwen Shen1, Qisheng Tang1
1Fudan University Huashan Hospital, Dept. of Neurosurgery, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science,Shanghai Medical College-Fudan University, Shanghai 200040, China.
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 O(6)-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.
Insights
BCNU/PLGA microspheres improved survival and reduced tumor growth in glioma-bearing mice. This treatment enhanced apoptosis and did not increase chemotherapy resistance, offering a promising therapeutic strategy.
Area of Science:
- Biomedical Engineering
- Oncology
- Drug Delivery Systems
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options.
- Chemotherapy resistance remains a significant challenge in managing brain gliomas.
- Local drug delivery systems aim to improve therapeutic efficacy and reduce systemic toxicity.
Purpose of the Study:
- To evaluate the efficacy of BCNU/PLGA (carmustine/poly(lactic-co-glycolic acid)) sustained-release microspheres.
- To assess the impact on tumor growth, apoptosis, and chemotherapy resistance in an orthotopic brain glioma model.
- To investigate the expression of key apoptosis and resistance markers (Bax, Bcl-2, MGMT).
Main Methods:
- BCNU/PLGA microspheres were prepared using a water-in-oil-in-water emulsion technique.
- GL261 glioma cells were implanted intracranially into C57BL/6 mice.
- Tumor volume was monitored via MRI, and survival rates were analyzed. Immunohistochemistry assessed Bax, Bcl-2, and MGMT expression.
Main Results:
- BCNU/PLGA microspheres significantly improved survival time and quality in tumor-bearing mice.
- MRI demonstrated tumor growth inhibition. The treatment increased the Bax/Bcl-2 ratio, indicating enhanced apoptosis.
- No significant change in O(6)-methylguanine-DNA methyltransferase (MGMT) expression was observed, suggesting no increased chemotherapy resistance.
Conclusions:
- Local implantation of BCNU/PLGA microspheres is an effective strategy for treating GL261 gliomas.
- The treatment improves survival, inhibits tumor proliferation, and induces apoptosis.
- BCNU/PLGA microspheres do not appear to increase chemotherapy resistance in this model.
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