Metformin Suppresses Metastatic Potential and Sensitizes Ovarian Cancer Cells to Chemotherapeutics

Vollständiger Abstract

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The failure of current therapeutics to elicit a durable response in metastatic ovarian cancer patients highlights the urgent need to develop more effective treatment strategies. In this study, we demonstrate that the anti-diabetic drug metformin exerts cytotoxic effects across a broad panel of ovarian cancer cell lines. Transcriptomic analyses revealed that, in addition to reducing cell viability and proliferation, metformin modulates pathways associated with metastatic progression, including cell migration, extracellular matrix remodeling, and cellular responses to chemotherapeutic agents. Consistent with these molecular changes, metformin significantly impaired ovarian cancer cell migration and invasion through Matrigel. Furthermore, metformin diminished the ability of ovarian cancer cells to form multicellular aggregates, a key property that facilitates successful metastatic dissemination within the peritoneal cavity. Although metformin produced only a modest increase in carboplatin sensitivity, systematic screening of FDA-approved drugs identified several agents whose efficacy was enhanced by metformin, including drugs not currently used to treat ovarian cancer. Collectively, these findings demonstrate that metformin suppresses metastatic phenotypes and enhances therapeutic vulnerability in ovarian cancer cells, supporting its potential repurposing as a combination therapy to improve treatment outcomes in ovarian cancer.