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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。
Objective To investigate the inhibitory effect of arsenic trioxide (As2O3) on glioma transplanted in nude mice and its mechanism. Methods The nude mice model of glioma was established and randomly divided into 3 groups: blank control group, PLGA group (50:50), PLGA group, arsenic trioxide-polylactic acid-glycolic acid (50:50) sustained-release agent group (As2O3-PLGA group). As2O3-PLGA group in the tumor built As2O3-PLGA one, the other groups were made the same intratumoral processing, the use of its role in the release of As2O3 observed tumor suppression. The apoptosis rate of the transplanted tumor was detected by TUNEL method. The protein expressions of Caspase-3 and Bcl-2 were detected by immunohistochemistry and Western-blot. Results There was no significant difference between the PLGA group and the blank control group (P> 0.05). The As2O3-PLGA group could significantly inhibit the growth of the subcutaneous tumor in nude mice (P <0.01), and the tumor inhibition rate was 60.8%. The apoptosis rate of tumor cells in As2O3-PLGA group (30.80%) was significantly higher than that in blank control group (3.92%) and PLGA group (4.08%). The content of Bcl-2 protein in the xenografts was significantly decreased and the content of Caspase-3 protein increased obviously. Conclusion As2O3 can significantly inhibit the growth of human gliomas in vivo and induce apoptosis of tumor cells. The molecular mechanism of As2O3 may be to down-regulate Bcl-2 protein expression and up-regulate the expression of Caspase-3 protein.