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

Turk J Biol. 2023 Aug 10;47(4):290-300. doi: 10.55730/1300-0152.2663. eCollection 2023.

Abstract

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 × 107 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-Prkdcscid/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 CO2 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.

Keywords: Colorectal cancer; IL-1; Notch; leptin; proangiogenic; proinflammatory.

Grants and funding

All funding for this study was supported by a grant from Eskişehir Osmangazi University Scientific Research Projects Committee (no: 201711028), Türkiye.