多西环素对荷瘤小鼠子宫内膜癌组织中CCAT1、MMP-2及TIMP-2表达的影响  

Effects of doxycycline on expressions of CCAT1,MMP-2 and TIMP-2 in endometrial carcinoma of tumor bearing mice

作　　者：魏旭静 李林[1] 张红真[1] 王景 徐静 WEI Xu-Jing;LI Lin;ZHANG Hong-Zhen;WANG Jing;XU Jing(Department of Obstetrics,the First Hospital of Hebei Medical University,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学第一医院产科,石家庄050000

出　　处：《中国免疫学杂志》2020年第21期2619-2623,共5页Chinese Journal of Immunology

基　　金：河北省卫计委医学科学研究项目(201904310)。

摘　　要：目的:探讨多西环素对小鼠子宫内膜癌组织中CCAT1、MMP-2及TIMP-2表达的影响。方法:将40只荷瘤小鼠随机分为模型组、多西环素低、中和高剂量组,每组10只。多西环素低、中和高剂量组分别腹腔注射盐酸多西环素5、10、20 mg/ml,模型组和对照组给予等量生理盐水,连续给药7 d。7 d后处死小鼠,剥离肿瘤称重,测定肿瘤抑制率,采用HE染色观察各组小鼠肿瘤组织病理变化情况。采用RT-PCR检测肿瘤组织CCAT1、MMP-2及TIMP-2 mRNA表达水平。免疫组化法检测各组MMP-2、TIMP-2、PCNA和Ki67表达水平以及MMP-2/TIMP-2比值。结果:与模型组相比,多西环素低、中、高剂量组小鼠肿瘤细胞体积明显减小,排列稀疏,多西环素组高剂量小鼠肿瘤细胞可见大面积坏死核碎裂,肿瘤抑制率明显上升(P<0.05),肿瘤组织MMP-2 mRNA和蛋白表达水平明显下降(P<0.05),TIMP-2 mRNA和蛋白表达水平明显升高(P<0.05),MMP-2/TIMP-2比值均明显下降(P<0.05),CCAT1、PCNA和Ki67表达水平均明显下降(P<0.05),多西环素各组的肿瘤抑制率、MMP-2 mRNA和蛋白表达水、TIMP-2 mRNA和蛋白表达水平、PCNA和Ki67蛋白表达水平差异有统计学意义(P<0.05)。结论:多西环素可能通过下调CCAT1、MMP-2,PCNA、Ki67表达,上调TIMP-2表达,对子宫内膜癌生长和肿瘤细胞增殖起抑制作用。Objective:To investigate the effect of doxycycline on the expressions of CCAT1,MMP-2 and TIMP-2 in endometrial carcinoma of the mice.Methods:40 tumor bearing mice were randomly divided into model group,low,medium and high dose doxycycline groups,10 mice in each group.Doxycycline hydrochloride 5,10,20 mg/ml were intraperitoneally injected into the low,medium and high dose doxycycline groups,while the control group and model group was given the same amount of normal saline for 7 days.The mice were sacrificed,the tumors were stripped and weighed,the tumor inhibition rates were determined,and the pathological changes of tumor tissues in each group were observed by HE staining after 7 days.Levels of CCAT1,MMP-2,TIMP-2,PCNA,Ki67 mRNA in tumor tissues were detected by RT-PCR.The expression levels of MMP-2,TIMP-2,PCNA,Ki67 and the ratio of MMP-2/TIMP-2 were detected by immunohistochemistry.Results:Compared with the model group,the tumor cells in the low,medium and high dose doxycycline group were significantly reduced in size and sparsely arranged,while large areas of necrotic nuclear fragmentation were observed in the high dose doxycycline group,and the tumor inhibition rate was significantly increased(P<0.05).The expression levels of MMP-2 mRNA and protein in tumor tissues were significantly decreased(P<0.05),TIMP-2 mRNA and protein were significantly increased(P<0.05),and the MMP-2/TIMP-2 ratio was significantly decreased(P<0.05).Expression levels of CCAT1,PCNA and Ki67 proteins in tumor tissues were significantly decreased(P<0.05).There were statistically significant differences in tumor inhibition rate,expression levels of MMP-2 mRNA and protein,expression levels of TIMP-2 mRNA and protein and levels of PCNA and Ki67 protein between the doxycycline groups(P<0.05).Conclusion:Doxycycline may inhibit the growth of endometrial cancer by down-regulating the expression levels of CCAT1,MMP-2,PCNA and Ki67,up-regulating the expression level TIMP-2.

关 键 词：多西环素 子宫内膜癌 CCAT1 MMP-2 TIMP-2 PCNA KI67 

分 类 号：R737.33[医药卫生—肿瘤]