Author:
Wu Bowen,Li Peng,Qiu Eryue,Chen Jian
Abstract
AbstractChemotherapy resistance hinders the successful treatment of osteosarcoma (OS) to some extent. Previous studies have confirmed that metformin (Met) enhances apoptosis induced by chemotherapeutic drugs, but the underlying mechanism remains unclear. To establish adriamycin (ADM)-resistant MG-63 (MG-63/ADM) cells, the dosage of ADM was progressively increased. The results of qRT-PCR and Western blotting demonstrated that the expression level of Yin Yang 1 (YY1) and multi-drug resistance-1 (MDR1) in MG-63/ADM cells were remarkably increased compared with those in MG-63 cells. Met dramatically enhanced ADM cytotoxicity and accelerated apoptosis of MG-63/ADM cells. Moreover, Met suppressed the expressions of YY1 and MDR1 in MG-63/ADM cells. YY1 promoted its transcriptional expression by directly binding to the MDR1 promoter. Furthermore, the effects of Met on ADM sensitivity in MG-63/ADM cells was reversed due to overexpression of YY1 or MDR1. Collectively, these findings suggested that Met inhibited YY1/MDR1 pathway to reverse ADM resistance in OS, providing a new insight into the mechanism of Met in ADM resistance of OS.
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Pharmacology
Reference34 articles.
1. Durfee RA, Mohammed M, Luu HH. Review of Osteosarcoma and Current Management. Rheumatol Ther. 2016;3:221–43.
2. Benini S, Baldini N, Manara MC, et al. Redundancy of autocrine loops in human osteosarcoma cells. Int J Cancer. 1999;80:581–8.
3. Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Cancer Treat Res. 2009;152:3–13.
4. Ye G, Huang M, Li Y, et al. The FAP alpha -activated prodrug Z-GP-DAVLBH inhibits the growth and pulmonary metastasis of osteosarcoma cells by suppressing the AXL pathway. Acta Pharm Sin B. 2022;12:1288–304.
5. Li Z, Wang L, Luo N, et al. Metformin inhibits the proliferation and metastasis of osteosarcoma cells by suppressing the phosphorylation of akt. Oncol Lett. 2018;15:7948–54.