Study Of Upregulation Of Matrix Metalloproteinase-2 Expression Mediated By ERK1/2/MAPK Signaling Pathway Promoting Drug Resistance In Osteosarcoma

Objective Multi-drug resistance (MDR) represents a major obstacle for chemotherapeutic treatment of osteosarcoma and the related mechanism of drug resistance is widely investigated. The aim of this study was to substantiate the potential mechanism"ERK1/2-MMP2". Methods In this experiment, the MG-63 osteosarcoma cell line with the property of MDR(called MG-63/R) was successfully constructed by the induce of high-dose ADM and then the part of MG-63/R(called MG-63/R+I) was intervented by PD98059( ERK1/2 inhibitor).We use cck-8 assay to detect cell proliferation and draw the growth curve.Meantime,the mRNA expression and protein translation of MMP-2 ,before and after blocking the activation of ERK1/2 ,was also detected by RT-PCR and Western Blot.Ultimately, the rate of apoptosis of MG-63/R cell and MG-63/R+I cell intervented by ADM in was determined by Annexin V/PI assay. Results The result of RT-PCR and Western Blot revealed that the mRNA expression and protein translation of MMP-2 in MG-63/R group was obviously more than MG-63 group;and also,the data of Annexin V/PI had clear distinction among MG-63,MG-63/R and MG-63/R+I group. Conclusion It is suggested that upregulation of matrix metalloproteinase-2 expression mediated by ERK1/2/MAPK signaling pathway promotes drug resistance in osteosarcoma.