Targeting of Notch, IL-1, and leptin has therapeutic potential in xenograft colorectal cancer

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Ozyurt R., Erkasap N., Ozkurt M., Erkasap S. M., Dımas K., Çakır Gündoğdu A., ...More

Turkish Journal of Biology, vol.47, no.4, pp.290-300, 2023 (SCI-Expanded) identifier identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 47 Issue: 4
  • Publication Date: 2023
  • Doi Number: 10.55730/1300-0152.2663
  • Journal Name: Turkish Journal of Biology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Veterinary Science Database, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.290-300
  • Eskisehir Osmangazi University Affiliated: Yes


Background/aim: Colorectal cancer (CRC) is a fatal malignancy type and its occurence still needs to be explored mechanistically. Notch, IL-1, and leptin crosstalk is reported to play a role in the proliferation, migration, and expression of proangiogenic molecules. In this study, we aimed to investigate the effect of inhibition of Notch, IL-1, and leptin on CRC. Materials and methods: To generate colorectal cancer tumor xenografts, 1 × 10 7 cells from exponentially growing cultures of HCT- 15 cells were injected subcutaneously, at the axillary region of the left and right rear flanks of forty $NOD.CB17-Prkd^{cscid}/J (NOD/SCID)$ female mice. The mice were then monitored for the development of tumors and were randomly divided into five groups when tumor sizes reached a volume of approximately 150 mm3. Mice were used to determine the effectiveness of the gamma-secretase inhibitor (DAPT, Notch inhibitor), the interleukin-1 receptor antagonist (Anakinra) and the leptin receptor antagonist (Allo aca) against tumor growth. The mice were euthanized by $CO_2$ inhalation immediately after the treatments finished, and all efforts were made to minimize suffering. Tumors were excissed for RT-PCR and histological analysis. Results: There is an intact Notch, IL-1, and leptin signaling axis, and in vivo antagonism of Notch, IL-1, and leptin affects mRNA and protein expression of inflammatory and angiogenic molecules. Conclusion: Present data suggest that targeting Notch, IL-1, and leptin may be possesses therapeutic potential in CRC.