Fudan University Huashan Hospital, Dept. of Neurosurgery, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science,Shanghai Medical College-Fudan University, Shanghai 200040, China.
Chin J Cancer Res. 2014 Feb;26(1):81-8. doi: 10.3978/j.issn.1000-9604.2014.02.01.
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.
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.
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).
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.
探讨用 BCNU/PLGA 微球治疗 C57BL/6 小鼠原位脑胶质瘤模型对肿瘤生长、细胞凋亡和化疗耐药的影响，细胞株为 GL261。
采用水包油包水乳化技术制备 BCNU/PLGA 缓释微球。立体定向技术将 GL261 细胞颅内注射入 C57BL/6 小鼠。将 60 只荷瘤小鼠随机均分为 3 组：未治疗对照组、PLGA 治疗组、BCNU/PLGA 治疗组。磁共振成像（MRI）评估肿瘤体积。接种后 2 周，治疗组植入 BCNU/PLGA 缓释片。观察生存时间和质量。采集标本，免疫组织化学染色检测 Bax、Bcl-2 和 O(6)-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）的表达。采用统计学方法分析相关数据。
成功制备并植入 BCNU/PLGA 缓释片。BCNU/PLGA 治疗组与对照组的生存时间有统计学差异（P<0.05）。MRI 扫描显示 BCNU/PLGA 对肿瘤生长有抑制作用。与 A 组和 B 组相比，BCNU/PLGA 降低了凋亡相关基因 Bcl-2 的表达（P<0.05），但未升高 Bax 的表达水平（P>0.05），Bax/Bcl-2 比值升高。MGMT 蛋白表达在治疗组无明显变化（P>0.05）。
局部植入 BCNU/PLGA 微球可显著提高 GL261 脑胶质瘤荷瘤小鼠的生存质量和时间，抑制肿瘤增殖，诱导更多细胞凋亡，且不会增加化疗耐药性。
