多西环素对乳腺癌移植瘤小鼠MMP2及TIMP2 mRNA表达影响.docVIP

多西环素对乳腺癌移植瘤小鼠MMP2及TIMP2 mRNA表达影响 　 作者：甘萍 李艾珊 聂桂丽 范英昌 【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。 【关键词】 多西环素；乳腺癌；基质金属蛋白酶2；金属蛋白酶组织抑制因子2 【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. 【Key words】Doxycycline; Breast cancer; Matrix metalloproteinase (MMP)2; Tissue inhibitor of metalloproteinase (TIMP)2 　　肿瘤患者的生存率与肿瘤的侵袭和转移密切相关，而细胞外基质(ECM) 的降解是肿瘤完成侵袭和转移的先决条件。基质金属蛋白酶(MMPs)在ECM的降解中起重要作用〔1〕。MMPs活性主要由基质金属蛋白酶组织抑制因子(TIMPs)调节。研究表明