https://doi.org/10.4081/ejh.2023.3612
Metformin sensitises osteosarcoma to chemotherapy via the IGF-1R/miR-610/FEN1 pathway
Submitted: 17 November 2022
Accepted: 13 May 2023
Published: 17 May 2023
Accepted: 13 May 2023
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
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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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Ethics Approval
This study was approved by the Ethics Committee of the Third Affiliated Hospital of Kunming Medical University and the Kunming Medical University Animal Care and Use Committee (Protocol no. YTH2019-026); all patients provided written informed consent and authorized biological specimen use, in accordance with the Declaration of Helsinki.Supporting Agencies
National Natural Science Foundation of China , Natural Science Foundation of Jiangsu Province, Basic Research Program of Xuzhou Health Commission, Development Foundation of Affiliated Hospital of Xuzhou Medical University, Applied basic research of Yunnan Science & Technology Agency-Joint Funds of Yunnan Science & Technology Agency and Kunming Medical UniversityHow to Cite
Dong, S., Xiao, Y., Zhu, Z., Ma, X., Peng, Z., Kang, J., … Li, Z. (2023). Metformin sensitises osteosarcoma to chemotherapy <em>via</em> the IGF-1R/miR-610/FEN1 pathway. European Journal of Histochemistry, 67(2). https://doi.org/10.4081/ejh.2023.3612
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