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Involvement of MMP-2 in Adriamycin Resistance Dependent on ERK1/2 Signal Pathway in Human Osteosarcoma MG-63 Cells

摘要Matrix metalloproteinase-2 (MMP-2) level and the ERK1/2 signal pathway are dependent factors for the growth and metastasis of cancer.However,the impact of MMP-2 in combination with ERK1/2 in tumor patients with drug resistance is unknown.To determine the relationship between MMP-2 and the ERK1/2 signal pathway,we established an adriamycin (ADM)-induced MG-63 (ADM-MG-63) cell line.With the increase of the ERK1/2 pathway blocker PD98059,we detected the expression levels of MMP-2 and p-ERK1/2 by Western blot in ADM-MG-63 cells.In ADM-MG-63 cells transfected with MMP-2-siRNA,the expression of ERK1/2 was detected for understanding the function of the ERK1/2 signal pathway.Three siRNAs for MMP-2 (MMP-2-siRNA) were designed,and the optimal one was selected and tested at different time points of 24,48 and 72 h.Under an ADM-induced condition,ADM-MG-63 cells were finally stable living in the medium of ADM (200 ng/mL).PD98059 could effectively suppress the expression levels of p-ERK1/2 and MMP-2.When the MMP-2 was silenced by using MMP-2-siRNA,the expression of p-ERK1/2 was enhanced.It is concluded that MMP-2 may be involved in ADM resistance dependent on ERK1/2 signal pathway,suggesting interference in ERK1/2 may be a new method of targeted therapy for tumor resistance.

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作者单位 Department of Orthopedics, Tongji Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [1]
分类号 R738
栏目名称 ORIGINAL ARTICLES
DOI 10.1007/sl1596-012-0014-x
发布时间 2012-05-16
基金项目
the Major State Basic Research Development of China
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