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Metformin sensitises osteosarcoma to chemotherapy via the IGF-1R/miR-610/FEN1 pathway

Metformin can enhance cancer cell chemosensitivity to anticancer drugs. IGF-1R is involved in cancer chemoresistance. The current study aimed to elucidate the role of metformin in osteosarcoma (OS) cell chemosensitivity modulation and identify its underlying mechanism in IGF-1R/miR-610/FEN1 signalli...

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Autores principales: Dong, Suwei, Xiao, Yanbin, Zhu, Ziqiang, Ma, Xiang, Peng, Zhuohui, Kang, Jianping, Wang, Jianqiang, Wang, Yunqing, Li, Zhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PAGEPress Publications, Pavia, Italy 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10230554/
https://www.ncbi.nlm.nih.gov/pubmed/37195011
http://dx.doi.org/10.4081/ejh.2023.3612
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author Dong, Suwei
Xiao, Yanbin
Zhu, Ziqiang
Ma, Xiang
Peng, Zhuohui
Kang, Jianping
Wang, Jianqiang
Wang, Yunqing
Li, Zhen
author_facet Dong, Suwei
Xiao, Yanbin
Zhu, Ziqiang
Ma, Xiang
Peng, Zhuohui
Kang, Jianping
Wang, Jianqiang
Wang, Yunqing
Li, Zhen
author_sort Dong, Suwei
collection PubMed
description Metformin can enhance cancer cell chemosensitivity to anticancer drugs. IGF-1R is involved in cancer chemoresistance. The current study aimed to elucidate the role of metformin in osteosarcoma (OS) cell chemosensitivity modulation and identify its underlying mechanism in IGF-1R/miR-610/FEN1 signalling. IGF-1R, miR-610, and FEN1 were aberrantly expressed in OS and participated in apoptosis modulation; this effect was abated by metformin treatment. Luciferase reporter assays confirmed that FEN1 is a direct target of miR-610. Moreover, metformin treatment decreased IGF-1R and FEN1 but elevated miR-610 expression. Metformin sensitised OS cells to cytotoxic agents, while FEN1 overexpression partly compromised metformin’s sensitising effects. Furthermore, metformin was observed to enhance adriamycin’s effects in a murine xenograft model. Metformin enhanced OS cell sensitivity to cytotoxic agents via the IGF-1R/miR-610/FEN1 signalling axis, highlighting its potential as an adjuvant during chemotherapy.
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spelling pubmed-102305542023-06-01 Metformin sensitises osteosarcoma to chemotherapy via the IGF-1R/miR-610/FEN1 pathway Dong, Suwei Xiao, Yanbin Zhu, Ziqiang Ma, Xiang Peng, Zhuohui Kang, Jianping Wang, Jianqiang Wang, Yunqing Li, Zhen Eur J Histochem Article Metformin can enhance cancer cell chemosensitivity to anticancer drugs. IGF-1R is involved in cancer chemoresistance. The current study aimed to elucidate the role of metformin in osteosarcoma (OS) cell chemosensitivity modulation and identify its underlying mechanism in IGF-1R/miR-610/FEN1 signalling. IGF-1R, miR-610, and FEN1 were aberrantly expressed in OS and participated in apoptosis modulation; this effect was abated by metformin treatment. Luciferase reporter assays confirmed that FEN1 is a direct target of miR-610. Moreover, metformin treatment decreased IGF-1R and FEN1 but elevated miR-610 expression. Metformin sensitised OS cells to cytotoxic agents, while FEN1 overexpression partly compromised metformin’s sensitising effects. Furthermore, metformin was observed to enhance adriamycin’s effects in a murine xenograft model. Metformin enhanced OS cell sensitivity to cytotoxic agents via the IGF-1R/miR-610/FEN1 signalling axis, highlighting its potential as an adjuvant during chemotherapy. PAGEPress Publications, Pavia, Italy 2023-05-17 /pmc/articles/PMC10230554/ /pubmed/37195011 http://dx.doi.org/10.4081/ejh.2023.3612 Text en ©Copyright: the Author(s), https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article
Dong, Suwei
Xiao, Yanbin
Zhu, Ziqiang
Ma, Xiang
Peng, Zhuohui
Kang, Jianping
Wang, Jianqiang
Wang, Yunqing
Li, Zhen
Metformin sensitises osteosarcoma to chemotherapy via the IGF-1R/miR-610/FEN1 pathway
title Metformin sensitises osteosarcoma to chemotherapy via the IGF-1R/miR-610/FEN1 pathway
title_full Metformin sensitises osteosarcoma to chemotherapy via the IGF-1R/miR-610/FEN1 pathway
title_fullStr Metformin sensitises osteosarcoma to chemotherapy via the IGF-1R/miR-610/FEN1 pathway
title_full_unstemmed Metformin sensitises osteosarcoma to chemotherapy via the IGF-1R/miR-610/FEN1 pathway
title_short Metformin sensitises osteosarcoma to chemotherapy via the IGF-1R/miR-610/FEN1 pathway
title_sort metformin sensitises osteosarcoma to chemotherapy via the igf-1r/mir-610/fen1 pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10230554/
https://www.ncbi.nlm.nih.gov/pubmed/37195011
http://dx.doi.org/10.4081/ejh.2023.3612
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