摘要目的：探讨沉默CD147基因对人乳腺癌MDA－MB－231细胞生长、增殖、运动能力的影响。方法构建CD147小干扰RNA（ siRNA）慢病毒载体并转染各实验组MDA－MB－231细胞，采用免疫细胞化学ABC法检测沉默前后MDA－MB－231细胞中CD147、基质金属蛋白酶（ MMP）－2、金属蛋白酶类组织抑制剂（ TIMP）－2蛋白的表达水平；采用即时定量PCR 和Western Blot 技术检测CD147、MMP－2、TIMP－2的mRNA和蛋白表达水平改变；采用CCK－8法和划痕实验分别检测细胞的增殖和迁移能力；建立裸鼠皮下移植瘤模型，观察CD147 siRNA对裸鼠瘤体质量和体积的影响。结果转染MDA－MB－231细胞后，CD147、MMP－2、TIMP－2蛋白呈弱阳性或阴性表达，明显低于对照组（ P＜0．01）。转染72 h时，CD147基因下调平均效率为96．03％±0．84％，MMP－2基因下调平均效率48．64％±0．35％，mRNA表达均明显下降（P＜0．05），而TIMP－2 mRNA表达水平与对照组相比差异无统计学意义（ P＞0．05）。转染第2天后， MDA－MB－231细胞生长明显受到抑制（ P ＜0．05）。转染24 h 后MDA－MB－231细胞平均迁移距离为（0．64±0．12） mm，而空白对照组细胞平均迁移距离为（4．69±0．85）mm，迁移速度减小。沉默CD147基因后，裸鼠瘤体体积和瘤体质量均下降（P＜0．05），平均瘤体质量为（1．85±0．98）g，移植瘤的生长受到抑制（P＜0．05）。结论 CD147可以影响MDA－MB－231细胞中的MMP－2／TIMP－2平衡，沉默CD147基因可以抑制MDA－MB－231细胞的增殖和迁移及裸鼠移植瘤的生长。

abstractsObjective To investigate the influence of siRNA-mediated down-regulation of CD147 on growth, proliferation and movement of human breast cancer cell line MDA-MB-231.Methods The protein expression of CD147, MMP-2 and TIMP-2 of the MDA-MB-231 cells were analyzed by ABC.Lentiviral expression vector of CD 147 gene was constructed and transfected into MDA-MB-231 cells.RT-PCR and Western blot were used to detect the mRNA and protein level changes of CD 147 genes to identify the optimal time point , followed by detection of changes of mRNA and protein expression of MMP-2 and TIMP-2 genes. CCK-8 reagent method and cell scratch test were used to detect the proliferation and migration change of MDA-MB-231 cells.The nude mouse model of breast cancer by hypodermic injection with MDA-MB-231 cells was established to document the effect of CD 147 siRNA on the tumor transplants.Results After transfection of lentiviral expression vector of CD 147 gene, protein of CD147, MMP-2 and TIMP-2 were weakly or negative expressed , significantly weaker than those of control group ( P<0.01 ) .After 72 hours of transfection, average down-regulation rate of CD147 and MMP-2 were 96.03%±0.84% and 96.03%± 0.84%, respectively.Both CD147 mRNA and MMP-2 mRNA expression were down-regulated(P<0.05), while TIMP-2 mRNA expression showed no significant deference ( P >0.05 ) .No less than 2 days after transfection, cell growth of MDA-MB-231 cell line was found significantly inhibited ( P <0.05 ) .After 24 hours of tranfection, average migration distance of MDA-MB-231 cell line and control group were (0.64 ±&nbsp;0.12)mm and (4.69 ±0.85)mm, respectively, which indicated a lower migrate speed.Down regulation of CD147 led to reduction of volume and mass of nude mouses .The growth of the carcinoma transplant was inhibited upon siRNA-mediated down-regulation of CD147 ( P <0.05 ) , with an average tumor mass of (1.85 ±0.98) g and both reduction of tumor size and tumor mass .Conclusions CD147 may alter the MMP-2/TIMP-2 balance in MDA-MB-231 cells. CD147 gene silencing inhibits the proliferation and migration of MDA-MB-231 cells and the growth of carcinoma transplants in nude mice .