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 Tunçdemir

doi:10.17944/interdiscip.1833817

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

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<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.

Keywords

Supporting Institution

No financial support was used by authors during this study.

Ethical Statement

This study was conducted exclusively on commercially available HepG2 hepatocellular carcinoma cell lines under in vitro conditions and did not involve human participants or animals; therefore, ethics committee approval was not required. Informed consent was also not applicable.

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Details

Primary Language

English

Subjects

Pharmacology and Pharmaceutical Sciences (Other), Cancer Cell Biology

Journal Section

Research Article

Authors

Tuğba Soydaş ^*
0000-0002-0684-1906
Türkiye

Merve Eskici
0000-0003-0581-7354
Türkiye

Matem Tunçdemir
0000-0002-5300-4449
Türkiye

Publication Date

August 23, 2026

Submission Date

December 1, 2025

Acceptance Date

June 28, 2026

Published in Issue

Year 2026 Volume: 17 Number: 58

DOI

https://doi.org/10.17944/interdiscip.1833817

IZ

https://izlik.org/JA47XC22EX

Cite

RIS / Bibtex

APA

Soydaş, T., Eskici, M., & Tunçdemir, M. (2026). Association of AP-1/c-Jun with IL-6 and IL-8 expression in hepatocellular carcinoma: attenuating effects of metformin in vitro. Interdisciplinary Medical Journal, 17(58), 158-165. https://doi.org/10.17944/interdiscip.1833817

AMA

1.Soydaş T, Eskici M, Tunçdemir M. Association of AP-1/c-Jun with IL-6 and IL-8 expression in hepatocellular carcinoma: attenuating effects of metformin in vitro. Interdiscip Med J. 2026;17(58):158-165. doi:10.17944/interdiscip.1833817

Chicago

Soydaş, Tuğba, Merve Eskici, and Matem Tunçdemir. 2026. “Association of AP-1 C-Jun With IL-6 and IL-8 Expression in Hepatocellular Carcinoma: Attenuating Effects of Metformin in Vitro”. Interdisciplinary Medical Journal 17 (58): 158-65. https://doi.org/10.17944/interdiscip.1833817.

EndNote

Soydaş T, Eskici M, Tunçdemir M (August 1, 2026) Association of AP-1/c-Jun with IL-6 and IL-8 expression in hepatocellular carcinoma: attenuating effects of metformin in vitro. Interdisciplinary Medical Journal 17 58 158–165.

IEEE

[1]T. Soydaş, M. Eskici, and M. Tunçdemir, “Association of AP-1/c-Jun with IL-6 and IL-8 expression in hepatocellular carcinoma: attenuating effects of metformin in vitro”, Interdiscip Med J, vol. 17, no. 58, pp. 158–165, Aug. 2026, doi: 10.17944/interdiscip.1833817.

ISNAD

Soydaş, Tuğba - Eskici, Merve - Tunçdemir, Matem. “Association of AP-1 C-Jun With IL-6 and IL-8 Expression in Hepatocellular Carcinoma: Attenuating Effects of Metformin in Vitro”. Interdisciplinary Medical Journal 17/58 (August 1, 2026): 158-165. https://doi.org/10.17944/interdiscip.1833817.

JAMA

1.Soydaş T, Eskici M, Tunçdemir M. Association of AP-1/c-Jun with IL-6 and IL-8 expression in hepatocellular carcinoma: attenuating effects of metformin in vitro. Interdiscip Med J. 2026;17:158–165.

MLA

Soydaş, Tuğba, et al. “Association of AP-1 C-Jun With IL-6 and IL-8 Expression in Hepatocellular Carcinoma: Attenuating Effects of Metformin in Vitro”. Interdisciplinary Medical Journal, vol. 17, no. 58, Aug. 2026, pp. 158-65, doi:10.17944/interdiscip.1833817.

Vancouver

1.Tuğba Soydaş, Merve Eskici, Matem Tunçdemir. Association of AP-1/c-Jun with IL-6 and IL-8 expression in hepatocellular carcinoma: attenuating effects of metformin in vitro. Interdiscip Med J. 2026 Aug. 1;17(58):158-65. doi:10.17944/interdiscip.1833817