三氧化二砷缓释剂瘤内治疗裸鼠胶质瘤的实验研究

目的探讨三氧化二砷(As2O3)对裸鼠移植胶质瘤的抑制作用及其作用机制。方法建立胶质瘤裸鼠移植模型,随机分为3组:空白对照组,缓释剂-聚乳酸-羟基乙酸聚合物(50:50)组(PLGA组)、三氧化二砷-聚乳酸-羟基乙酸聚合物(50:50)缓释剂组(As2O3-PLGA组)。As2O3-PLGA组在瘤内置入As2O3-PLGA一片,其他每组均作相同的瘤内置入处理,利用其缓释As2O3的作用观察肿瘤的抑制情况。并用TUNEL法检测移植瘤的细胞凋亡率,用免疫组化染色及Western-blot检测Caspase-3与Bcl-2的蛋白表达。结果PLGA组对肿瘤无明显抑制作用,与空白对照组差异无统计学意义(P>0.05);As2O3-PLGA组能明显抑制裸鼠皮下肿瘤生长(P<0.01),抑瘤率为60.8%。As2O3-PLGA组的肿瘤细胞凋亡率(30.80%)明显高于空白对照组(3.92%)及PLGA组(4.08%)。移植瘤组织中Bcl-2蛋白含量明显减少,Caspase-3蛋白含量明显增加。结论As2O3对体内胶质瘤的生长具有明显的抑制作用,并能诱导肿瘤细胞部分凋亡,其作用的分子机制可能是下调Bcl-2蛋白表达,上调Caspase-3蛋白表达。

Experimental study of As2O3 retarder treatment to the intratumoral nude mouse

Objective To study the inhibitory effect and the mechanism of arsenic trioxide ( As2O3) in rats bearing transplanted glioma. Methods We built up the subcutaneous brain glioma models of rats, then they were divided into 3 groups randomly: control group, PLGA group (50: 50 ) and As2 O3 -PLGA group. In As2O3-PLGA group , we implanted a wafer of As2O3-PLGA into transplantable tumor , nothing in control group and vacant PLGA in PLGA group. To observe the inhibitory effect of As2O3 on glioma by As2O3 -PLGA releasing As2O3, TUNEL test was used to check the cell apoptosis rate of glioma cell, Western-blot test was used to detect the expression level of Caspase-3 and Bcl-2 protein. Results The PLGA group have no obviously inhibitory effect to glioma, there is no obvious difference compared with the vacant control group (P > 0. 05) ;As2O3-PLGA has obvious inhibitory effect on growing glioma in the model of rats bearing transplantable glioma ( P < 0. 01) , and the inhibitory rate reaches 60. 8% . Apoptpsis rate of glioma in As2O3-PLGA group(30. 8% ) is significantly higher than control group(3. 92% ) and PLGA group (4.08% ). In As2O3-PLGA group, As2O3 induced a decreasing in level of Bcl-2 protein and an increasing in level of Caspase-3 protein after application of the As2O3-PLGA wafer. Conclusion As2O3 has obvious inhibitory effect on the growth of glioma in the model of rats and induced tumor cells apoptosis, the molecule mechanism may is the decrease of Bcl-2 protein expression and enhancement of Caspase-3 protein expression.