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

Kolorektal Kanserde İrinotekan Sitotoksisitesini Arttırmak için TGF-Β Sinyalizasyonunun Modülasyonu

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

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
Sayfa
14–20
Yayın Tarihi
2026-03-03
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⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

Bulgular: LY2109761 ve irinotekanın kombinasyon tedavisi, HCT-116 hücrelerinde hücre canlılığını doza ve zamana bağlı bir şekilde önemli ölçüde azalttı.

📌 3 Maddede Bu Makale

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Amaç & Hipotez:Amaç: Bozulmuş Transforme edici büyüme faktörü beta (Transforming Growth Factor Beta, TGF-β) sinyalizasyonu kolorektal kanser (CRC) ilerlemesine katkıda bulunur.
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Temel Bulgular & Veri:TGF-β reseptörlerini (TGFβR) bilinen kemoterapilerle birlikte hedeflemek tedavi etkinliğini artırabilir.
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Sonuç & Katkı:Bulgular: LY2109761 ve irinotekanın kombinasyon tedavisi, HCT-116 hücrelerinde hücre canlılığını doza ve zamana bağlı bir şekilde önemli ölçüde azalttı.
🔬Tür:Deneysel Tarla Denemesi
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Kolorektal kanser · TGFβR-I/II · İrinotekan

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

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.

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Bu Makaleye Atıf Yap

Ay, E. N., Sarıman, M., Acar, M. (2026). Kolorektal Kanserde İrinotekan Sitotoksisitesini Arttırmak için TGF-Β Sinyalizasyonunun Modülasyonu. Harran Üniversitesi Tıp Fakültesi Dergisi, Cilt: 23 Sayı: 1, 14–20. https://doi.org/10.35440/hutfd.1622831

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Kaynakça (37)

  1. Gupta S. Screening for Colorectal Cancer. Hematol Oncol Clin North Am. 2022;36(3):393-414.
  2. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-63.
  3. Roshandel G, Ghasemi-Kebria F, Malekzadeh R. Colorectal Cancer: Epidemiology, Risk Factors, and Prevention. Cancers (Basel). 2024;16(8):1530.
  4. GBD 2019 Colorectal Cancer Collaborators. Global, regional, and national burden of colorectal cancer and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Gastroenterol Hepatol. 2022;7(7):627-47.
  5. International Agency for Research on Cancer. World Health Organisation [https://www.iarc.who.int/]. Data visualization tools for exploring the global cancer burden in 2022 Online Resources. Available from: https://gco.iarc.who.int/media/globocan/factsheets/populations/792-turkiye-fact-sheet.pdf (https://gco.iarc.fr/en).
  6. Smith HG, Nilsson PJ, Shogan BD, Harji D, Gambacorta MA, Romano A, et al. Neoadjuvant treatment of colorectal cancer: comprehensive review. BJS Open. 2024;8(3):zrae038.
  7. Jiao J, Wu Y, Wu S, Jiang J. Enhancing Colorectal Cancer Treatment Through VEGF/VEGFR Inhibitors and Immunotherapy. Curr Treat Options Oncol. 2025;26(3):213-25.
  8. Shi J, Sun Z, Gao Z, Huang D, Hong H, Gu J. Radioimmunotherapy in colorectal cancer treatment: present and future. Front Immunol. 2023;14:1105180.
  9. de Man FM, Goey AKL, van Schaik RHN, Mathijssen RHJ, Bins S. Individualization of Irinotecan Treatment: A Review of Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics. Clin Pharmacokinet. 2018 Oct;57(10):1229-54.
  10. Jiang W, Liu Q, Yang D, Yang SB. The efficacy of irinotecan supplementation for colorectal cancer: A meta-analysis of randomized controlled studies. Medicine (Baltimore). 2022;101(41):e28090.
  11. Paulík A, Nekvindová J, Filip S. Irinotecan toxicity during treatment of metastatic colorectal cancer: focus on pharmacogenomics and personalized medicine. Tumori. 2020;106(2):87-94.
  12. Kok SY, Nakayama M, Morita A, Oshima H, Oshima M. Genetic and nongenetic mechanisms for colorectal cancer evolution. Cancer Sci. 2023;114(9):3478-86.
  13. Yan H, Jiang F, Yang J. Association of β-Catenin, APC, SMAD3/4, Tp53, and Cyclin D1 Genes in Colorectal Cancer: A Systematic Review and Meta-Analysis. Genet Res (Camb). 2022;2022:5338956.
  14. Inamura K. Colorectal Cancers: An Update on Their Molecular Pathology. Cancers (Basel). 2018;10(1):26.
  15. Derynck R, Budi EH. Specificity, versatility, and control of TGF-β family signaling. Sci Signal. 2019;12(570):eaav5183.
  16. Li X, Wu Y, Tian T. TGF-β Signaling in Metastatic Colorectal Cancer (mCRC): From Underlying Mechanism to Potential Applications in Clinical Development. Int J Mol Sci. 2022;23(22):14436.
  17. Feng Y, Pauklin S. Two Sides of the Same Coin: The Roles of Transforming Growth Factor-β in Colorectal Carcinogenesis. Gastroenterology. 2020;159(1):397-98.
  18. Shan H, Tian G, Zhang Y, Qiu Z. Exploring the molecular mechanisms and therapeutic potential of SMAD4 in colorectal cancer. Cancer Biol Ther. 2024;25(1):2392341.
  19. Zhang BH, Wang C, Dong W, Chen X, Leng C, Luo X, et al. A novel approach for monitoring TGF-β signaling in vivo in colon cancer. Carcinogenesis. 2021;42(4):631-9.
  20. Zhou J, Jiang W, Huang W, Ye M, Zhu X. Prognostic Values of Transforming Growth Factor-Beta Subtypes in Ovarian Cancer. Biomed Res Int. 2020;2020:2170606.
  21. Wang J, Xiang H, Lu Y, Wu T. Role and clinical significance of TGF β1 and TGF βR1 in malignant tumors (Review). Int J Mol Med. 2021;47(4):55.
  22. Zhang M, Kleber S, Röhrich M, Timke C, Han N, Tuettenberg J, et al.Blockade of TGF-β signaling by the TGFβR-I kinase inhibitor LY2109761 enhances radiation response and prolongs survival in glioblastoma. Cancer Res. 2011;71(23):7155-67.
  23. Gao Y, Shan N, Zhao C, Wang Y, Xu F, Li J et al.LY2109761 enhances cisplatin antitumor activity in ovarian cancer cells. Int J Clin Exp Pathol. 2015;8(5):4923-32.
  24. Ghasemi M, Turnbull T, Sebastian S, Kempson I. The MTT Assay: Utility, Limitations, Pitfalls, and Interpretation in Bulk and Single-Cell Analysis. Int J Mol Sci. 2021;22(23):12827.
  25. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-8.
  26. Colak S, Ten Dijke P. Targeting TGF-β Signaling in Cancer. Trends Cancer. 2017;3(1):56-71.
  27. White RA, Malkoski SP, Wang XJ. TGFβ signaling in head and neck squamous cell carcinoma. Oncogene. 2010;29(40):5437-46.
  28. Papageorgis P. TGFβ Signaling in Tumor Initiation, Epithelial-to-Mesenchymal Transition, and Metastasis. J Oncol. 2015;2015:587193.
  29. Xue VW, Chung JY, Córdoba CAG, Cheung AH, Kang W, Lam EW, et al.Transforming Growth Factor-β: A Multifunctional Regulator of Cancer Immunity. Cancers (Basel). 2020;12(11):3099.
  30. Donovan J, Slingerland J. Transforming growth factor-beta and breast cancer: Cell cycle arrest by transforming growth factor-beta and its disruption in cancer. Breast Cancer Res. 2000;2(2):116-24.
  31. Baba AB, Rah B, Bhat GR, Mushtaq I, Parveen S, Hassan R, et al.Transforming Growth Factor-Beta (TGF-β) Signaling in Cancer-A Betrayal Within. Front Pharmacol. 2022;13:791272.
  32. Yoshida K, Matsuzaki K, Murata M, Yamaguchi T, Suwa K, Okazaki K. Clinico-Pathological Importance of TGF-β/Phospho-Smad Signaling during Human Hepatic Fibrocarcinogenesis. Cancers (Basel). 2018;10(6):183.
  33. Katz LH, Li Y, Chen JS, Muñoz NM, Majumdar A, Chen J, et al. Targeting TGF-β signaling in cancer. Expert Opin Ther Targets. 2013;17(7):743-60.
  34. Kim BG, Malek E, Choi SH, Ignatz-Hoover JJ, Driscoll JJ. Novel therapies emerging in oncology to target the TGF-β pathway. J Hematol Oncol. 2021;14(1):55.
  35. Ciardiello D, Elez E, Tabernero J, Seoane J. Clinical development of therapies targeting TGFβ: current knowledge and future perspectives. Ann Oncol. 2020;31(10):1336-1349.
  36. Huynh LK, Hipolito CJ, Ten Dijke P. A Perspective on the Development of TGF-β Inhibitors for Cancer Treatment. Biomolecules. 2019;9(11):743.
  37. Paulík A, Nekvindová J, Filip S. Irinotecan toxicity during treatment of metastatic colorectal cancer: focus on pharmacogenomics and personalized medicine. Tumori. 2020;106(2):87-94.