王婧1,2 陈信义1,2 侯丽1,2△ 刘朝阳3 陆鸿飞1,2 刘伟1,2.茶多酚对Lewis 肺癌小鼠移植瘤MMP-2、TIMP-2 表达的影响[J].现代生物医学进展英文版,2012,12(10):1837-1841. |
茶多酚对Lewis 肺癌小鼠移植瘤MMP-2、TIMP-2 表达的影响 |
Effects of Tea Polyphenols on the Expression of MMP-2 and TIMP-2 inLewis Lung Carcinoma Xenografted in C57BL/6 Mice |
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DOI: |
中文关键词: 茶多酚 肺癌 基质金属蛋白酶-2 组织金属蛋白酶抑制剂-2 |
英文关键词: Tea polyphenols Lewis lung carcinoma MMP-2 TIMP-2 |
基金项目:北京中医药大学自主选题项目(2009JYBZZ-JS067) |
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中文摘要: |
目的:观察茶多酚对肺癌小鼠移植瘤基质金属蛋白酶-2(MMP-2)及其相应的组织金属蛋白酶抑制剂-2(TIMP-2)表达的影
响,探讨茶多酚抗新生血管生成的效应机制。方法:建立57 小鼠肺癌移植瘤模型,测定茶多酚低、高剂量组以及茶多酚联合沙利
度胺组的肿瘤抑制率,并且采用免疫组化法检测各组MMP-2、TIMP-2 表达水平以及MMP-2/TIMP-2 比值,以探讨其抗肿瘤的分
子机制。结果:实验表明,茶多酚有如下作用:①沙利度胺组、茶多酚低剂量组、茶多酚高剂量组、茶多酚低剂量联合沙利度胺组、
茶多酚高剂量联合沙利度胺组的肿瘤抑制率分别为17.26 %、16.94 %、20.81 %、21.94 %和44.32 %,茶多酚高剂量联合沙利度胺
组与模型组瘤重比较,有统计学意义(P<0.05);②茶多酚各组及联合用药各组能下调肿瘤组织MMP-2 蛋白表达,茶多酚高剂量
联合沙利度胺组能上调TIMP-2 蛋白表达,与模型对照组比较,均具有统计学意义(P<0.05);③用药各组MMP-2/TIMP-2 比值均
有所下降,茶多酚各组明显降低,茶多酚大剂量联合沙利度胺组比值下降最为显著。结论:茶多酚高剂量联合沙利度胺组对肺癌
有明显抑制作用。其机制可能与下调MMP-2 表达、上调TIMP-2 表达、调整MMP-2/TIMP-2 比值失衡状态,从而抗肺癌新生血管
生成相关。 |
英文摘要: |
Objective: To observe the effect of Tea Polyphenols (TP) on the expression of matrix metalloproteinase-2 (MMP-2)
and its corresponding tissue inhibitor of metalloproteinase-2 (TIMP-2) in Lewis lung cancer xenograft in mice, so as to explore TP's
anti-angiogenesis mechanism. Methods: Lewis lung carcinoma was successfully implanted in 48 C57BL/6 mice, which were then
randomly divided into six groups namely model control group, Thalidomide control group, TP low-dose group, TP high-dose group, TP
low-dose combined with Thalidomide group and TP high dose combined with Thalidomide group. Tumor inhibition rates of these groups
were examined, while MMP-2 and TIMP-2 expression was detected applying immunohistochemical technique and MMP-2/TIMP-2 ratio
was calculated, in order to investigate the molecular mechanism of TP's anti-tumor effect. Results: According to our study, TP was
proved to have the following effects: (1) The tumor inhibition rates of Thalidomide control group, TP low-dose group, TP high-dose
group, TP low-dose plus Thalidomide group and TP high dose plus Thalidomide group were 17.26%, 16.94%, 20.81%, 21.94%, 44.32%
respectively. Compared with model control group, the tumor inhibition rate rise in TP high dose plus Thalidomide group was of statistical
difference (P<0.05). (2) Compared with model control group, the expression of MMP-2 was significantly down-regulated in all four
groups containing TP (P<0.05), while TIMP-2 expression in TP high dose plus Thalidomide group was up-regulated (P<0.05). (3) The
MMP-2/TIMP-2 ratio was reduced in every treatment group, and the ratio of TP high dose plus Thalidomide group was most obviously
decreased. Conclusion: TP high dose plus Thalidomide can significantly inhibit Lewis lung cancer growth. And one of its possible
mechanisms is to down-regulate MMP-2 expression, up-regulate TIMP-2 expression, reduce MMP-2/TIMP-2 ratio to normal range, thus
play a important role in anti-angiogenesis process. |
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