LY2109761 Potentiates 5-FU-Induced Cytotoxicity in HCT 116 Cells and Preserves PBMC Viability In Co-Culture Models

Ebru Nur Ay; Sarehan Akyüz; Ayşenur Kokoglu; Günnur Deniz; Ferda Kaleağasıoğlu

doi:10.17776/csj.1972130

LY2109761 Potentiates 5-FU-Induced Cytotoxicity in HCT 116 Cells and Preserves PBMC Viability In Co-Culture Models

Abstract

Colorectal cancer remains a leading cause of cancer-related mortality worldwide, with chemoresistance representing a major therapeutic challenge. The transforming growth factor-beta (TGF-β) signaling pathway contributes to tumor progression and treatment resistance, making it a promising target for combination therapy. This study investigated whether the dual TGF-β receptor I/II inhibitor LY2109761 enhances the cytotoxic effects of 5-fluorouracil (5-FU) in colorectal cancer cells while assessing its impact on immune cell viability. Cell viability was determined by MTT assay following treatment with 5-FU and LY2109761, alone or in combination, in HCT 116 colorectal cancer cells. Preliminary Bliss independence analysis indicated a localized positive interaction at selected concentrations; however, the limited concentration matrix precludes a definitive conclusion regarding pharmacological synergy. Exploratory ELISA analyses revealed non-significant changes in TGF-β and TGF-βR2 levels following treatment. Because downstream TGF-β signaling was not directly assessed, these findings should not be interpreted as mechanistic evidence of pathway inhibition. Nevertheless, LY2109761 enhanced the cytotoxic activity of 5-FU under selected concentration conditions and did not markedly increase apoptotic death in PBMCs, supporting further mechanistic and preclinical investigation of this proof-of-concept combination strategy.

Keywords

5-FU, Coculture, HCT 116, LY2109761, PBMC, TGF-β receptor inhibitor

Supporting Institution

Istanbul University

Ethical Statement

This study was approved by the Istinye University Human Research Ethics Committee (Meeting No: 2025/04; Protocol No: 2025-195; Approval Date: May 20, 2025). All procedures involving human participants and peripheral blood mononuclear cells (PBMCs) were conducted in accordance with the ethical standards of the institutional research committee and the principles of the Declaration of Helsinki.

Thanks

This research was supported by Istinye University Scientific Research Projects (2023/B10).

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Details

Primary Language

English

Subjects

Cell Development, Proliferation and Death, Cancer Biology

Journal Section

Research Article

Authors

Ebru Nur Ay ^*
0000-0001-7121-4362
Türkiye

Sarehan Akyüz
0009-0004-0038-4793
Türkiye

Ayşenur Kokoglu
0000-0002-5596-9746
Türkiye

Günnur Deniz
0000-0002-0721-6213
Türkiye

Ferda Kaleağasıoğlu
0000-0003-1511-0432
Türkiye

Publication Date

October 27, 2026

Submission Date

June 18, 2026

Acceptance Date

September 14, 2026

Published in Issue

Year 2026 Volume: 47 Number: 5

DOI

https://doi.org/10.17776/csj.1972130

IZ

https://izlik.org/JA66YP96GD

APA

Ay, E. N., Akyüz, S., Kokoglu, A., Deniz, G., & Kaleağasıoğlu, F. (2026). LY2109761 Potentiates 5-FU-Induced Cytotoxicity in HCT 116 Cells and Preserves PBMC Viability In Co-Culture Models. Cumhuriyet Science Journal, 47(5), 860-870. https://doi.org/10.17776/csj.1972130

AMA

1.Ay EN, Akyüz S, Kokoglu A, Deniz G, Kaleağasıoğlu F. LY2109761 Potentiates 5-FU-Induced Cytotoxicity in HCT 116 Cells and Preserves PBMC Viability In Co-Culture Models. CSJ. 2026;47(5):860-870. doi:10.17776/csj.1972130

Chicago

Ay, Ebru Nur, Sarehan Akyüz, Ayşenur Kokoglu, Günnur Deniz, and Ferda Kaleağasıoğlu. 2026. “LY2109761 Potentiates 5-FU-Induced Cytotoxicity in HCT 116 Cells and Preserves PBMC Viability In Co-Culture Models”. Cumhuriyet Science Journal 47 (5): 860-70. https://doi.org/10.17776/csj.1972130.

EndNote

Ay EN, Akyüz S, Kokoglu A, Deniz G, Kaleağasıoğlu F (October 1, 2026) LY2109761 Potentiates 5-FU-Induced Cytotoxicity in HCT 116 Cells and Preserves PBMC Viability In Co-Culture Models. Cumhuriyet Science Journal 47 5 860–870.

IEEE

[1]E. N. Ay, S. Akyüz, A. Kokoglu, G. Deniz, and F. Kaleağasıoğlu, “LY2109761 Potentiates 5-FU-Induced Cytotoxicity in HCT 116 Cells and Preserves PBMC Viability In Co-Culture Models”, CSJ, vol. 47, no. 5, pp. 860–870, Oct. 2026, doi: 10.17776/csj.1972130.

ISNAD

Ay, Ebru Nur - Akyüz, Sarehan - Kokoglu, Ayşenur - Deniz, Günnur - Kaleağasıoğlu, Ferda. “LY2109761 Potentiates 5-FU-Induced Cytotoxicity in HCT 116 Cells and Preserves PBMC Viability In Co-Culture Models”. Cumhuriyet Science Journal 47/5 (October 1, 2026): 860-870. https://doi.org/10.17776/csj.1972130.

JAMA

1.Ay EN, Akyüz S, Kokoglu A, Deniz G, Kaleağasıoğlu F. LY2109761 Potentiates 5-FU-Induced Cytotoxicity in HCT 116 Cells and Preserves PBMC Viability In Co-Culture Models. CSJ. 2026;47:860–870.

MLA

Ay, Ebru Nur, et al. “LY2109761 Potentiates 5-FU-Induced Cytotoxicity in HCT 116 Cells and Preserves PBMC Viability In Co-Culture Models”. Cumhuriyet Science Journal, vol. 47, no. 5, Oct. 2026, pp. 860-7, doi:10.17776/csj.1972130.

Vancouver

1.Ebru Nur Ay, Sarehan Akyüz, Ayşenur Kokoglu, Günnur Deniz, Ferda Kaleağasıoğlu. LY2109761 Potentiates 5-FU-Induced Cytotoxicity in HCT 116 Cells and Preserves PBMC Viability In Co-Culture Models. CSJ. 2026 Oct. 1;47(5):860-7. doi:10.17776/csj.1972130

As of 2026, Cumhuriyet Science Journal will be published in six issues per year, released in February, April, June, August, October, and December

LY2109761 Potentiates 5-FU-Induced Cytotoxicity in HCT 116 Cells and Preserves PBMC Viability In Co-Culture Models

Abstract

Keywords

Supporting Institution

Ethical Statement

Thanks

References

Details

Primary Language

Subjects

Journal Section

Authors

Publication Date

Submission Date

Acceptance Date

Published in Issue

DOI

IZ

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