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125I粒子对人结肠腺癌(SW480)裸鼠皮下移植瘤增殖与凋亡的影响

The Experimental Study of the Influence of Proliferation and Apoptosis in Nude Mice Bearing SW480 Tumor Treated with Iodine-125 Brachytherapy

【作者】 李滢旭

【导师】 罗开元; 杨镛;

【作者基本信息】 昆明医学院 , 外科学, 2010, 硕士

【摘要】 目的:通过建立人中分化结肠腺癌细胞(SW480)裸鼠皮下移植瘤模型,从增殖与凋亡两方面探讨碘-125(1251)粒子治疗中分化结肠腺癌的有效性及科学性。方法:将人结肠腺癌(SW480)细胞种植到雄性BALB/c-nu/nu裸小鼠皮下建立动物模型,随机将荷瘤裸小鼠分成对照组和实验组(每组24只),对照组与实验组各自再随机分成4组(每组6只),对照组植入空白粒子,实验组植入剂量为0.4mCi的125I粒子(1mCi=3.7×107Bq),观察粒子植入后瘤体生长情况,分别在植入后第7天、14天、21天、28天;按顺序处死实验组与对照组中第1、2、3、4组荷瘤裸鼠。剥取瘤体,分别用于流式细胞仪检测肿瘤细胞周期的再分布,免疫组化SP法测定增殖细胞核抗原的表达,透射电镜观察肿瘤细胞超微结构的改变,原位末端标记法检测肿瘤细胞原位凋亡情况。结果:随着放射时间的积累,流式细胞仪检测实验组肿瘤细胞周期被阻滞在G2/M期。增殖细胞核抗原标记指数(labelling index, LI)在第一周后,实验组中表达显著低于对照组(P<0.05),透射电镜示:实验组可见早中晚期凋亡细胞,对照组肿瘤细胞生长良好,少见细胞凋亡。TUNEL检测肿瘤细胞原位凋亡情况,实验组从第二周以后凋亡指数(Apoptosis index,AI)显著高于对照组,差异有统计学意义(P<0.05)。结论:1.125I粒子通过持续低剂量辐射使人中分化结肠腺癌(SW480)细胞周期阻滞在G2/M期,并下调PCNA的表达,是抑制人中分化结肠腺癌(SW480)增殖的重要生物学机制之一。2.125I粒子持续低剂量辐射可诱导人中分化结肠腺癌细胞(SW480)凋亡增加,且存在时-效关系。

【Abstract】 Ojective:To discuss the effectiveness and scientific in nude mice bearing SW480 tumor treated with Iodine-125 brachytherapy.Methods:Taked the male nude mice of BLAB/c-nu/nu inoculated with human colon adenocarcinoma(SW480) cell as animal model. To be implanted iodine-125 seeds,the animal were divided into two groups (n=24), control groups and experiment group then randomly divided into 4 groups again (n=6).control group:to be implanted empty seeds, without iodine-125 radioelement(OmCi); experiment group:to be implanted iodine-125 seeds (0.4mCi),We observe the condition of tumor growth after implanted iodine-125. we killed 6 nude mice of each group in 7th、14th、21th、28th day after implantation, then we tested these implanted tumors by flow cytometer, transmission electron microscopy immunohistochemical and TUNEL respectively. Results:With the accumulation of radiation time, the tumor cells cycle in experiment group was blocked in G2/M phase.we can observe the early-mid-late period cell apoptosis in the experiment group by TEM,rare cell apoptosis were found in the control group. PCNA in the experiment group was significantly lower expression than it in corresponding control group after 1st week.(P<0.05). TUNEL was used to detect apoptosis in situ. After the second week, the apoptosis index in the experiment group were significantly higher than the control group.Conclusions:1.one of the important biological mechanism to restrain the colon adenocarcinoma (SW480)is the iodine-125 seeds continuous low-dose radiationwas to block the cell cycle in G2/M phase and the proliferating cell nuclear antigen was inhibited.2. The continuous radiation in a low-doses with the iodine-125 seeds could induced cell apoptotic and exist the relationship of time-effect.

  • 【网络出版投稿人】 昆明医学院
  • 【网络出版年期】2010年 08期
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