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Matrix metalloproteinase-3 promotes the proliferation and invasion of osteosarcoma MG-63 cells and its possible mechanism
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Abstract:
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.
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Project Supported:
Project supported by the Science and Technology Project of Jiangxi Province (No. 20121BBG70038)
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