骨唾液酸蛋白基因沉默抑制乳腺癌细胞与骨基质粘附  

Inhibitory effect of bone sialoprotein silencing on the adhesion ability of breast cancer cells to bone matrix

作　　者：王丽[1,2] 王捷[2] 杨德猛[1,2] 杨传红[2] 夏冰[2] 王江涛[2] 冼江[2] 

机构地区：[1]华南理工大学生物科学与工程学院,广州510006 [2]广州军区广州总医院医学实验科,广州510010

出　　处：《生物工程学报》2011年第2期233-239,共7页Chinese Journal of Biotechnology

基　　金：广东省自然科学基金项目(No.06104396)资助~~

摘　　要：旨在探索骨唾液酸蛋白(Bone sialoprotein,BSP)基因沉默对亲骨转移乳腺癌细胞(MDA-MB-231BO)与骨基质粘附能力的影响,为以BSP为靶点的乳腺癌骨转移预防和靶向治疗提供实验依据。体外检测BSP基因沉默对乳腺癌细胞与小鼠骨基质粘附能力的影响,MTS法检测细胞增殖能力;扫描电镜观察骨片表面肿瘤细胞粘附情况和骨吸收状况;ELISA法检测骨基质细胞粘附培养上清中TGF-β1和RANKL表达分泌量差异;左心室注射法构建裸鼠骨转移模型,检测不同细胞株在裸鼠体内转移能力。结果提示BSP基因沉默可抑制亲骨转移乳腺癌细胞与骨基质粘附能力和增殖能力。亲骨转移乳腺癌细胞易与骨基质发生粘附,粘附部位可见骨吸收造成的骨基质破坏。BSP基因沉默引起部分细胞表面形态的改变,并对TGF-β1和RANKL的表达和分泌具有抑制作用。裸鼠骨组织X线检查和HE染色结果显示,沉默BSP基因可在一定程度上抑制骨转移发生和转移灶发展。结果证实BSP基因沉默可抑制亲骨转移乳腺癌细胞增殖、骨基质粘附,影响细胞表面形态,进而抑制骨转移。We performed this research mainly to explore the effect of bone sialoprotein（BSP） silence by siRNA on the adhesion ability to bone matrix of bone-seeking breast cancer cells（MDA-MB-231BO）.Also we aimed to provide experimental data for prevention and treatment of breast cancer bone metastasis by targeting BSP.We explored the effects of BSP gene silence on characteristics of bone-seeking breast cancer cells： proliferation by MTS[3-（4,5-dimethylthiazol-2-yl）-5-（3-carboxymethoxyphenyl）-2-（4-sulfophenyl）-2H-tetrazolium,inner salt] assay,bone adhesion ability by a mouse bone adhesion model in vitro,morphology of the cells by SEM,and secretion of transforming growth factor-β1（TGF-β1） and receptor activator of nuclear factor-kappa B ligand（RANKL） by ELISA kits.We performed intra-cardiac injection in nude mice to explore bone metastatic ability of different cell lines.The results showed that knockdown of BSP significantly inhibited the proliferation of MDA-MB-231BO cells and their adhesion to bone matrix.We also observed bone destruction caused by bone resorption around some adhering cells.The appearances of the cells changed in BSP gene silenced group,and the secretion of TGF-β1 and RANKL decreased.The results showed BSP gene silence can partial inhibition bone metastasis of breast cancer cells in nude mice by X-ray assay and hematoxylin-eosin staining.Based on our research,siRNA-mediated BSP silencing can inhibit proliferation and adhesion to bone matrix of bone-seeking breast cancer cells and change their surface structure,thus inhibits their bone metastatic ability.

关 键 词：骨唾液酸蛋白 基因沉默 乳腺癌 骨转移 骨基质粘附 

分 类 号：R737.9[医药卫生—肿瘤]