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多西环素对乳腺癌移植瘤小鼠MMP-2及TIMP-2 mRNA表达的影响

Effects of doxycycline on mRNA expressions of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in breast cancer with lung metastasis model mice

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【作者】 甘萍李艾珊聂桂丽范英昌

【Author】 GAN Ping,LI Ai-Shan,NIE Gui-Li,et al.Department of Pathology,Tianjin Medical College,Tianjin 300222,China

【机构】 天津医学高等专科学校病理教研室天津中医药大学

【摘要】 目的研究多西环素在小鼠乳腺癌肺转移模型中对基质金属蛋白酶-2(MMP-2)及金属蛋白酶组织抑制因子-2(TIMP-2)mRNA表达的影响。方法30只TAⅡ近交系小鼠建立肺转移性乳腺癌BCML-TAⅡ99模型,随机分为对照组及给药组,每组15只,于可触及肿物后次日,给药组腹腔注射盐酸多西环素0.1 ml(10 mg/ml),对照组给予等量生理盐水。7 w后处死动物,剥离肿瘤称重,部分新鲜组织采用逆转录多聚酶链反应(RT-PCR)方法检测肿瘤组织MMP-2及TIMP-2 mRNA表达水平。结果多西环素给药组小鼠肿瘤生长大小及转移率分别为(2.718±0.337)g和13.3%均低于对照组〔(4.313±0.468)g,53.3%,P<0.01,P<0.05〕。与对照组比较,多西环素治疗组MMP-2 mRNA为0.637±0.088,明显低于对照组(1.035±0.097,P<0.05);TIMP-2 mRNA为0.778±0.148,明显高于对照组(0.484±0.125,P<0.05)。结论多西环素通过调节MMP-2及TIMP-2 mRNA的表达水平,对小鼠乳腺癌肺转移模型中肿瘤生长及转移发挥抑制作用。

【Abstract】 Objective To study effect and mechanism of doxycycline on the mRNA expressions of matrix metalloproteinase(MMP)-2 and tissue inhibitor of metalloproteinase(TIMP)-2 in breast cancer with lung metastasis model mice(BCML-TAⅡ99).Methods 30 TAⅡ99 mice of breast cancer models with lung metastasis were randomly divided into doxycycline treatment group and control group.Mice in treatment group were injected with doxycycline and those in control group with physiological saline solution everyday when tumor could be touched.7 weeks later,all mice were killed.All tumors were peeled off and weighted,then small parts of tumors were used to detect the expressions of MMP-2 mRNA and TIMP-2 mRNA by the RT-PCR.Results Both tumor weight and metastasis rate in treatment group were lower than those of control group(P<0.05).The expression of MMP-2 mRNA was lower and the expression of TIMP-2 mRNA was higher in treatment group than that of control group(P<0.05).Conclusions Doxycycline can inhibit tumor growth and metastasis in breast cancer with lung metastasis model mice by regulating MMP-2 mRNA and TIMP-2 mRNA expression.

【基金】 天津市高等学校科技发展基金计划项目(20060124)
  • 【文献出处】 中国老年学杂志 ,Chinese Journal of Gerontology , 编辑部邮箱 ,2010年02期
  • 【分类号】R737.9
  • 【被引频次】15
  • 【下载频次】184
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