Metformin suppresses breast cancer growth via inhibition of cyclooxygenase‑2
Bin Shi, Xinyu Hu, Huimin He, Wenzheng Fang
Abstract
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 <em>in vitro</em> and suppressed tumor growth <em>in vivo</em>. 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 <em>in vitro</em> and <em>in vivo</em> 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.