Involvement of MMP-2 in adriamycin resistance dependent on ERK1/2 signal pathway in human osteosarcoma MG-63 cells.

Abstract

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.

• Authors: Ye Ren, Fengjing Guo, Anmin Chen, Rui Deng, Jiang Wang
• Journal: Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban (J Huazhong Univ Sci Technolog Med Sci) Vol. 32 Issue 1 Pg. 82-86 (Feb 2012) ISSN: 1672-0733 [Print] China
• PMID: 22282250 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Doxorubicin
• Matrix Metalloproteinase 2

Topics

• Antibiotics, Antineoplastic (therapeutic use)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Doxorubicin (therapeutic use)
• Drug Resistance, Neoplasm
• Humans
• MAP Kinase Signaling System (drug effects)
• Matrix Metalloproteinase 2 (metabolism)
• Osteosarcoma (drug therapy, metabolism, pathology)
• Treatment Outcome