目的：研究基质金属蛋白酶-3（matrix metalloproteinase-3，MMP-3）对骨肉瘤细胞增殖、侵袭的影响，并初步探讨MMP-3促进骨肉瘤侵袭和转移的机制。方法:收集2013年1月1日至2013年11月1日期间解放军第184医院骨科收治的骨肉瘤患者40例和健康人40名的血液标本，ELISA法检测其中MMP-3含量，并采用SPSS软件分析MMP-3含量与骨肉瘤Enneking分期的相关性。RT-PCR分别检测不同骨肉瘤细胞株U2-OS、HOS-143b、MG-63中MMP-3的表达。MTT法、Transwell侵袭实验观察50、100、200 ng/ml MMP-3刺激或转入MMP-3- shRNA慢病毒（MOI=50、100、200）对MG-63细胞增殖和侵袭的影响，Western blotting方法检测MMP-3过表达或沉默对MG-63细胞中侵袭、转移相关的蛋白p-AKT、核蛋白NF-κB表达的影响。〖HT5W〗结果：骨肉瘤患者血清中MMP-3的含量高于正常人(F=186.4, P=0.000)；且MMP-3含量与骨肉瘤Enneking分期成正相关(r=0.736，P=0.043)。与其他3株细胞相比，MG-63细胞株中MMP-3表达最高（t=5.12, P<0.05）。 MMP-3刺激导致MG-63细胞内MMP-3过表达，p-AKT和核内NF-κB表达升高，并促进MG-63细胞的增殖和侵袭；转入MMP-3- shRNA慢病毒导致MMP-3表达沉默，p-AKT和核内NF-κB表达降低，抑制MG-63细胞的增殖和侵袭。结论： MMP-3可能通过增加AKT磷酸化水平和促进NF-κB核转位来促进骨肉瘤细胞的增殖和侵袭。

Objective: To explore the influence and the mechanism of matrix metalloproteinase-3 (MMP-3) on invasion and metastasis of osteosarcoma. Methods: 40 cases of patients with osteosarcoma in No. 184 Hospital of PLA from January 1, 2013 to November 1, 2013 and 40 cases of healthy people were collected , and the serum of the patients with osteosarcoma and the healthy people were collected and the content of MMP-3 was detected with ELISA. And, the correlation between MMP-3 and the pathogenesis of osteosarcoma was also analyzed by SPSS. The mRNA levels of MMP-3 were detected by the method of RT-PCR in different osteosarcoma cell lines such as U2-OS，HOS-143b，MG-63cell lines. The proliferation of MG-63 after given different concentration of MMP-3 or knockdown MMP-3 was detected using MTT assay. And the invasion ability was detected by Transwell. Finally, the MMP-3 promotes the invasion and metastasis related proteins of osteosarcoma such as p-AKT, NF-κB were detected by Western blotting. Results: MMP-3 was highly expression in the serum of the patients with osteosarcoma (F=186.4, P=0.000), and there was a strong positive correlation between MMP-3 exepression and Enneking stage in osteosarcoma(r=0.736, P=0.043). MMP-3 was highly expression in the cell lines of MG-63 (P<0.05). The overexpression of MMP-3 stimulated by MMP-3 cultivation increased the expression of p-AKT and the intranuclear NF-κB, then promoted the proliferation and invasion ability of MG-63 cells (P<0.05); In contrast, MMP-3- shRNA transfection knockdown the MMP-3, result in reduction of the expression of p-AKT and the intranuclear NF-κB, then suppressed the proliferation and invasion ability of MG-63 cells (P<0.05). Conclusion: MMP-3 promotes the invasion and metastasis of osteosarcoma may via increasing the phosphorylation of AKT and promoting the translocation of NF-κB1.

江西省科技计划资助项目（No. 20121BBG70038）。