抑制CXCR4活性对乳腺癌骨转移影响的体内外研究  

In vivo and in vitro studies of blocking CXC chemokine receptor-4 on bone metastasis of breast cancer

作　　者：肖丹[1] 刘寿贵[1] 刘磊[1] 郭善禹[1] 

机构地区：[1]上海交通大学医学院附属第九人民医院普外科,上海200011

出　　处：《中国肿瘤生物治疗杂志》2012年第6期609-614,共6页Chinese Journal of Cancer Biotherapy

基　　金：上海市教育委员会科研基金资助项目(No.09yz79)~~

摘　　要：目的:应用特异性抑制剂AMD3100抑制人乳腺癌骨高转移MDA-MB-231SA-rfp细胞中CXCR4的活性,探讨CX-CR4在乳腺癌细胞体内、外增殖和迁移中的作用和机制。方法:CCK8法和Transwell法检测AMD3100对MDA-MB-231SA-rfp细胞体外增殖和迁移能力的影响。构建MDA-MB-231SA-rfp细胞骨转移裸鼠模型,以不同质量浓度的AMD3100处理后,X线影像观察骨转移情况,进一步利用MicroPET进行半定量分析,并应用H-E染色检测骨转移灶的定位。Western blotting法检测AMD3100对MDA-MB-231SA-rfp细胞和移植瘤转移灶组织中CXCR4蛋白表达的影响。结果:AMD3100能明显抑制MDA-MB-231SA-rfp细胞在SDF-1刺激下的增殖和迁移(P<0.05),较高质量浓度(2 000 ng/ml)的AMD3100效果更明显(P<0.01)。成功构建MDA-MB-231SA-rfp细胞裸鼠乳腺癌转移模型,不同质量浓度AMD3100处理后,小鼠下肢骨骨质破坏程度降低;MicroPET分析发现,对照组、低剂量AMD3100组、高剂量AMD3100组SUVmax值分别为9.44±0.53、5.70±0.25、2.18±0.47(P<0.01);组织病理检测证实为乳腺癌骨转移灶。Western blotting结果显示,AMD3100作用前后MDA-MB-231SA-rfp细胞和骨转移灶标本中CXCR4蛋白表达无明显变化。结论:AMD3100降低CXCR4的活性能抑制乳腺癌MDA-MB-231SA-rfp细胞体外增殖和迁移能力,并能抑制裸鼠体内乳腺癌骨转移灶的形成。Objective： To investigate the effect and mechanism of CXC chemokine receptor4 （CXCR4） in the prolif- eration and migration of breast cancer MDA-MB-231SA-rfp cells in vitro and in vivo by a specific small CXCR4 inhibitor, AMD3100. Methods： MDA-MB-231SA-rfp cells were treated with AMD3100, and the proliferation and migration were detected by CCK-8 and Transwell assay. MDA-MB-231SA-rfp cells were inoculated into nude mice to establish a model of breast cancer bone metastasis xenograft. AMD3100 at different final concentrations were delivered to mice. X-ray was taken to observe breast cancer bone metastasis and MicroPET was used to perform a semiquatitative analysis of breast canc- er bone metastasis. H-E staining was used to further determine the location of breast cancer bone metastasis. Western blot- ting was performed to determine CXCRd protein expression in MDA-MB-231SA-rfp cells as well as in xenograft tissues be- fore and after AMD3100 administration. Results： The cell proliferation and migration of MDA-MB-231SA-rfp cells line in- duced by SDF-1 were significantly inhibited by AMD3100 （ P 〈 0.05 ） and 2 000 ng/ml AMD3100 showed much more sig- nificant inhibition of the cell proliferation and migration （ P 〈 0.01 ）. The model of breast cancer bone metastasis xenograft was successfully established. Bone erosion of the lower limb found by X-ray was decreased after AMD3100 treatment of different concentrations . MicroPET images demonstrated that SUVmax values of the control group, low concentration AMD3100 group and high concentration AMD3100 group were respectively 9.44 ±0.53, 5.70 ± 0.25 and 2.18 ± 0.47 （ P 〈 0.01 ）. H-E staining detection confirmed the bone metastasis of breast cancer. No significant difference was found inCXCR4 protein expression in MDA-MB-231SA-rfp cells and bone metastasis tissues before and tion. Conclusion： Blocking the CXCR4 activity by AMD3100 can inhibit the proliferation and cancer MDA-MB-231SA-rfp cells in vitro, and also the bone metastasis in xenogra

关 键 词：CXC趋化因子受体4 AMD3100 乳腺癌 骨转移 MICROPET 

分 类 号：R737.9[医药卫生—肿瘤] R730.5[医药卫生—临床医学]