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Association of AP-1/c-Jun with IL-6 and IL-8 expression in hepatocellular carcinoma: attenuating effects of metformin in vitro

Tuğba Soydaş, Merve Eskici, Matem Tunçdemi̇r

Interdisciplinary Medical Journal, 2026

Abstract

Objective: Hepatocellular carcinoma remains a major contributor to cancer mortality worldwide, with low five-year survival rates despite treatments, underscoring the need for more effective and targeted therapies. Metformin, an oral antihyperglycemic agent, has gained attention for its potential anticancer properties. The present study aims to investigate the effects of metformin on key inflammatory cytokines involved in hepatocellular carcinoma (HCC) progression, as well as on the expression of c-Jun, a key subunit of the AP-1.Method: HepG2 cells were treated with metformin at a range of concentrations from 500 μM to 10 mM for 24 hours. To evaluate the anticancer effects of metformin, cell viability was assessed using the trypan blue exclusion method, while IL-6 and IL-8 concentrations were quantified by ELISA. Furthermore, c-Jun protein expression was examined by immunocytochemistry.Results: Metformin treatment led to a significant reduction in the levels of IL-6 and IL-8 in HepG2 cells compared to control group (p

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