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Journals / Harran Üniversitesi Tıp Fakültesi Dergisi / 2026 / Cilt: 23 Sayı: 1

Modulation of TGF-Β Signaling to Enhance Irinotecan Cytotoxicity in Colorectal Cancer

Kolorektal Kanserde İrinotekan Sitotoksisitesini Arttırmak için TGF-Β Sinyalizasyonunun Modülasyonu

Ebru Nur Ay(İstinye Üniversitesi)0000-0001-7121-4362
Melda Sarıman(İSTANBUL GALATA ÜNİVERSİTESİ, DİŞ HEKİMLİĞİ FAKÜLTESİ)0000-0003-0898-529X
Muradiye Acar(İSTİNYE ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0003-4357-5229
Pages
14–20
Publication Date
2026-03-03
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Conclusions: The combination of LY2109761 and irinotecan exhibited enhanced cytotoxicity compared to irinotecan alone, suggesting this approach as a promising therapeutic strategy for CRC.

📌 3 Key Takeaways

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Objective & Hypothesis:Background: Impaired Transforming Growth Factor Beta (TGF-β) signaling contributes to colorectal cancer (CRC) progression.
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Key Findings & Data:This study investigates the effects of a TGFβR-I/II inhibitor (LY2109761) on the cytotoxic activity of irinotecan in the human colorectal cancer cell line HCT-116.
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Conclusion & Impact:Conclusions: The combination of LY2109761 and irinotecan exhibited enhanced cytotoxicity compared to irinotecan alone, suggesting this approach as a promising therapeutic strategy for CRC.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:Kolorektal kanser · TGFβR-I/II · İrinotekan

Abstract

Background: Impaired Transforming Growth Factor Beta (TGF-β) signaling contributes to colorectal cancer (CRC) progression. Targeting TGF-β receptors (TGFβR) in combination with established chemotherapies may enhance treatment efficacy. This study investigates the effects of a TGFβR-I/II inhibitor (LY2109761) on the cytotoxic activity of irinotecan in the human colorectal cancer cell line HCT-116. Materials and Methods: LY2109761 was used to pharmacologically inhibit TGFβR-I/II in HCT-116 cells. Cell viability following treatment with irinotecan, LY2109761, or their combination was assessed using the MTT assay. Real-time quantitative polymerase chain reaction (RT-qPCR) quantified mRNA levels of genes associated with cell death, cell cycle, and TGF-β signaling. Results: Combination therapy of LY2109761 and irinotecan significantly reduced cell viability in HCT-116 cells in a dose- and time-dependent manner. Enhanced expression of cell cycle inhibitor P21 and increased markers of apoptosis and autophagy were observed. Conclusions: The combination of LY2109761 and irinotecan exhibited enhanced cytotoxicity compared to irinotecan alone, suggesting this approach as a promising therapeutic strategy for CRC.

Özet

Amaç: Bozulmuş Transforme edici büyüme faktörü beta (Transforming Growth Factor Beta, TGF-β) sinyalizasyonu kolorektal kanser (CRC) ilerlemesine katkıda bulunur. TGF-β reseptörlerini (TGFβR) bilinen kemoterapilerle birlikte hedeflemek tedavi etkinliğini artırabilir. Amacımız insan kolorektal kanser hücre hattı HCT-116'da TGFβR-I/II inhibitörü (LY2109761) ile irinotekanın sitotoksik aktivitesine olan etkilerinin belirlenmesidir. Materyal ve metod: HCT-116 hücrelerinde TGFβR-I/II'yi farmakolojik olarak inhibe etmek için LY2109761 inhibitörü kullanıldı. MTT analizleri, irinotekan, LY2109761 ve bunların kombinasyonu ile tedaviden sonraki hücre canlılığı değerlendirildi. Kantitatif Real Time PCR (RT-qPCR) ile, hücre ölümü, hücre döngüsü ve TGF-β sinyalizasyonu ile ilişkili genlerin mRNA düzeyleri değerlendirildi. Bulgular: LY2109761 ve irinotekanın kombinasyon tedavisi, HCT-116 hücrelerinde hücre canlılığını doza ve zamana bağlı bir şekilde önemli ölçüde azalttı. Hücre döngüsü inhibitörü P21'in artan ekspresyonu ve apoptoz ve otofaji belirteçlerinin arttığı gözlemlendi. Sonuç: LY2109761 ve irinotekanın kombinasyonu, irinotekanın tek başına kullanımına kıyasla artan sitotoksisite sonucu CRC için umut verici bir tedavi stratejisi olduğunu göstermektedir. Anahtar Kelimeler: Kolorektal kanser, TGFβR-I/II, İrinotekan, LY2109761, Sitotoksisite

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Cite This Article

Ay, E. N., Sarıman, M., Acar, M. (2026). Modulation of TGF-Β Signaling to Enhance Irinotecan Cytotoxicity in Colorectal Cancer. Harran Üniversitesi Tıp Fakültesi Dergisi, Cilt: 23 Sayı: 1, 14–20. https://doi.org/10.35440/hutfd.1622831

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