Metformin Alleviates Adriamycin Resistance of Osteosarcoma by Declining YY1 to Inhibit MDR1 Transcriptional Activity

Overview

Journal BMC Pharmacol Toxicol

Publisher Biomed Central

Specialty Pharmacology

Date 2023 Oct 12

PMID 37828612

Authors

Bowen Wu

Peng Li

Eryue Qiu

Jian Chen

Affiliations

Soon will be listed here.

Abstract

Chemotherapy 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.

Citing Articles

Using β-Elemene to reduce stemness and drug resistance in osteosarcoma: A focus on the AKT/FOXO1 signaling pathway and immune modulation.

Zhang S, Xing Z, Ke J J Bone Oncol. 2025; 50():100655.

PMID: 39850453 PMC: 11755076. DOI: 10.1016/j.jbo.2024.100655.

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