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

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 sig...

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Published in:Journal of Huazhong University of Science and Technology. Medical sciences 2012-02, Vol.32 (1), p.82-86
Main Author: 任晔 郭风劲 陈安民 邓睿 王江
Format: Article
Language:English
Subjects:
adriamycin
matrix
Antibiotics, Antineoplastic - therapeutic use
Cell Line, Tumor
Cell Survival - drug effects
Doxorubicin - therapeutic use
Drug Resistance, Neoplasm
Humans
interference
MAP Kinase Signaling System - drug effects
Matrix Metalloproteinase 2 - metabolism
Medicine
Medicine & Public Health
metalloproteinase-
osteosarcoma
RNA
Osteosarcoma - drug therapy
Osteosarcoma - metabolism
Osteosarcoma - pathology
Treatment Outcome
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Summary: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 con-cluded that MMP-2 may be involved in ADM resistance dependent on ERK1/2 signal pathway,sug-gesting interference in ERK1/2 may be a new method of targeted therapy for tumor resistance.
ISSN:1672-0733
1993-1352
DOI:10.1007/s11596-012-0014-x