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乳腺癌裸鼠移植瘤NES1基因去甲基化治疗 被引量:2

Demethylation treatment of NES1 gene for breast carcinoma xenografted in nude mice
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摘要 目的研究5-杂氮-2′-脱氧胞嘧啶核苷对乳腺癌裸鼠移植瘤的抗肿瘤效应。方法建立人乳腺癌裸鼠移植瘤模型,观察5-氮-2′-脱氧胞苷的抗肿瘤作用。10只裸鼠随机分为治疗组(5-氮-2′-脱氧胞苷组)和对照组(PBS组),测定用药前后两组肿瘤的体积变化,计算抑瘤率并绘制肿瘤生长曲线;采用免疫组化及蛋白印迹方法检测肿瘤中正常上皮细胞特异性基因1(NES1)蛋白表达。结果治疗组与对照组比较,其抑瘤率为57.44%,具有显著差异(P<0.01)。用5-氮-2′-脱氧胞苷治疗后,HE染色可见对照组瘤细胞生长活跃,核分裂像多见,未见坏死,治疗组肿瘤细胞变性、坏死严重,细胞核浓缩、碎裂;免疫组化染色及蛋白印迹结果均表明NES1基因蛋白的表达明显增高。结论NES1基因可作为一种肿瘤抑制基因和分子标志物,其表达缺失与乳腺癌的发生、发展密切相关。使用去甲基化药物可使NES1基因表达增高,从而发挥抑瘤作用,为乳腺癌的治疗开辟了一条新途径。 Objective To study the anti-tumor effect of 5-aza-2'-deoxycytidine (5-aza-dC) on breast carcinoma xenografted in nude mice. Methods The model of breast carcinoma xenografted in nude mice was established. Ten mice were randomized into the treatment group ( treated with 5-aza-dC) and control group ( treated with PBS). The mass of the tumors before and after treatment were measured in the two groups, and the inhibition rate of the tumor was calculated and the growth curve was drawn. Immunohistochemistry and Western blotting were employed to detect the expression of normal epithelial cell specific-1 ( NES1 ) gene. Results The inhibition rate of the tumor in the treatment group was 57.44% , which was significantly different from the control group(P 〈 0.01 ). Results from immunohistochemistry and Western blotting indicated that the expression of NES1 gene was significantly increased after the treatmeat with 5-aza-dC. Conclusion NES1 gene may serve as an anti-tumor gene and molecular marker, whose absence is closely related with the carcinogenesis and development of breast carcinoma. Demethylation treatment may increase the expression of NES1 gene and bring the anti-tumor effect, which paves a new way for the treatment of breast carcinoma.
出处 《上海交通大学学报(医学版)》 CAS CSCD 北大核心 2007年第1期72-75,共4页 Journal of Shanghai Jiao tong University:Medical Science
基金 教育部留学回国人员科研启动基金(2003-406)~~
关键词 乳腺肿瘤 正常上皮细胞特异性1基因 5-氮-2′-脱氧胞苷 breast carcinoma normal epithelial cell specific-1 gene 5-aza-2'-deoxycytidine
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