Metformin alleviates adriamycin resistance of osteosarcoma by declining YY1 to inhibit MDR1 transcriptional activity

BMC Pharmacology and Toxicology

Research

Jian Chen¹  Bowen Wu¹  Peng Li¹  Eryue Qiu² 

[1] Department of Orthopedics, Zhuzhou central hospital, 116 Changjiangnan Road, Tianyuan District, 412007, Zhuzhou, Hunan, China;Trauma center, Zhuzhou central hospital, 412007, Zhuzhou, Hunan, China;

关键词: Osteosarcoma;    Metformin;    Adriamycin resistant;    Yin Yang 1;    Multi-drug resistance-1;   

DOI  :  10.1186/s40360-023-00685-8

 received in 2022-11-28, accepted in 2023-09-02,  发布年份 2023

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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