Tugba SOYDAS, Merve ESKICI, Matem TUNCDEMIR
Interdisciplinary Medical Journal - 2026;17(58):158-165
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 muM 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<0.05). These pro-inflammatory cytokines are associated with cancer cell proliferation, angiogenesis, and metastatic potential, suggesting that metformin may exert anti-cancer effects through modulation of the inflammatory microenvironment. Furthermore, immunocytochemical analysis revealed a marked decrease in c-Jun protein expression in metformin-treated cells, indicating potential downregulation of the AP-1 transcriptional pathway, which plays a pivotal role in cancer progression and cell survival. Conclusion : These findings suggest that metformin suppresses pro-inflammatory cytokine expression in HepG2 cells, which may be associated with reduced c-Jun levels. The results provide preliminary in vitro evidence that warrants further investigation into metformin's role in HCC models.
