Involvement of MMP-2 in Adriamycin Resistance Dependent on ERK1/2 Signal Pathway in Human Osteosarcoma MG-63 Cells
10.1007/sl1596-012-0014-x
- Author:
REN YE
1
;
GUO FENGJING
;
CHEN ANMIN
;
DENG RUI
;
WANG JIANG
Author Information
1. Department of Orthopedics, Tongji Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Keywords:
adriamycin;
matrix metalloproteinase-2;
osteosarcoma;
RNA interference
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2012;32(1):82-86
- CountryChina
- Language:Chinese
-
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.
