三氧化二砷抑制乳腺癌裸鼠移植瘤的生长及其作用机制的探讨
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刘连新

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Arsenic trioxide inhibition of tumor growth of subcutaneously implanted human breast cancer cells and its mechanism
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    摘要:

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    目的 探讨三氧化二砷(As2O3)对人乳腺癌细胞系MCF7细胞裸鼠背部皮下移植瘤生长的抑制作用及其作用机制。
    方法 建立BALB/Cnu/nu裸鼠MCF7人乳腺癌皮下移植瘤模型,以不同浓度的As2O3行腹腔内注射,与5氟脲尿嘧啶(5FU)治疗进行对比,观察移植瘤的瘤重及瘤重抑制率。通过流式细胞仪检测移植瘤的凋亡情况,免疫组织化学法检测bcl2,Fas基因表达水平的变化,并进行血常规及骨髓涂片检查。
    结果 5FU(8mg/kg)组,As2O3 (4mg/kg)组,As2O3(8mg/kg)组均能明显抑制裸鼠皮下肿瘤的生长,抑瘤率分别为38.33%,51.42%和62.43%;As2O3对移植瘤的生长抑制作用明显强于5FU,差异有显著性 (P<0.01)。两种浓度As2O3组MCF7细胞凋亡率明显高于5FU组。各实验组乳腺癌细胞存在G2/M期阻滞,在G1峰前出现明显的凋亡峰。移植瘤组织中bcl2蛋白阳性细胞数明显减少,Fas蛋白阳性细胞数明显增加。血常规及骨髓涂片计数显示As2O3实验组未见造血系统功能受抑,与5FU组相比较,差异有显著性(P<0.05)。
    结论 As2O3可明显抑制乳腺癌移植瘤的生长,诱导移植瘤MCF7细胞凋亡;其作用的机制可能是下调bcl2基因表达,上调Fas基因表达。

    Abstract:

    Abstract:Objective To study the inhibitory effect of arsenic trioxide(As2O3) on the tumor growth of breast cancer cell line MCF7 implanted subcutaneously in nude mice and its mechanism.
    Methods BALB/Cnu/nu nude mice were subcutaneously injected with MCF7 breast cancer cell line, and treated with intraperitoneal injection of As2O3 and 5FU in different concentrations. The implanted tumor was weighed, and the tumor inhibition rates were calculated. The apoptosis of the implanted tumor was detected by flow cytometry. The expressions of bcl2 and Fas induced by As2O3 were examined by immunohistochemical method. Routine blood test and bone marrow test were used to observe the function of hematopoietic system after As2O3 treatment.
    Results The growth of implanted tumor was markedly inhibited with 5FU, low dose and high dose As2O3, the inhibitory rates being 38.33%、51.42% and 62.43%,respectively. The inhibitory effect of As2O3 was significantly stronger than that of 5FU(P<0.01). The apoptosis rate of MCF7 cells treated with the 2 concentrations of As2O2 was significantly higher than that of 5FU treated group. Breast cancer cells in all the study groups showed G2/M stage arrest, while a marked apoptosis peak was observed before the G1 peak. The immunohistochemical staining showed that the number of bcl2 protein positive cells decreased, and the number of Fas protein positive cells increased. The function

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曲志博,刘连新 ,陈炜,郭化鑫,杨海彦,潘尚哈,姜洪池.三氧化二砷抑制乳腺癌裸鼠移植瘤的生长及其作用机制的探讨[J].中国普通外科杂志,2007,16(1):21-.
DOI:10.7659/j. issn.1005-6947.2007.01.021

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  • 收稿日期:2006-06-17
  • 最后修改日期:2006-10-26
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  • 在线发布日期: 2007-01-25