Metformin suppresses breast cancer growth via inhibition of cyclooxygenase‑2
- Bin Shi
- Xinyu Hu
- Huimin He
- Wenzheng Fang
Affiliations: Department of Medical Oncology, Fuzhou General Hospital of Fujian Medical University, East Hospital Affiliated to Xiamen University (The 900th Hospital of The Joint Logistics Support Force of The Chinese PLA), Dongfang Hospital, Xiamen University, Fuzhou, Fujian 350025, P.R. China
- Published online on: June 23, 2021 https://doi.org/10.3892/ol.2021.12876
Copyright: © Shi
et al. This is an open access article distributed under the
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Pre‑clinical and on‑going trials have indicated the advantage of using metformin as an anticancer drug alone or in combination with other chemotherapeutics for the treatment of patients with breast cancer. However, the mechanisms by which metformin attenuates tumorigenesis remain to be further elucidated. The present study investigated the anticancer effects of metformin in breast cancer and identified potential molecular targets of metformin using western blotting and immunohistochemical analysis. Metformin significantly decreased tumor cell proliferation in vitro and suppressed tumor growth in vivo. Moreover, it induced the activation of AMP‑induced protein kinase and suppression of phosphorylated‑eukaryotic translation initiation factor 4E‑binding protein 1 (p‑4E‑BP1), a downstream effector of the mTOR signaling pathway, and decreased cyclin D1 levels in in vitro and in vivo experimental models. Additionally, metformin inhibited cyclooxygenase (COX)‑2 expression. Clinically, high expression levels of COX‑2 and p‑4E‑BP1 in tissues of patients with breast cancer were significantly associated with enhanced lymphatic metastasis and distant metastasis. Thus, the current data suggested that metformin may have potential value as a synergistic therapy targeting both the COX‑2 and mTOR signaling pathways.