COG 133

COG 133



Intestinal mucositis is one of the major troublesome side effects of cancer chemotherapy leading to poor patient compliance. In this study we address the role of the new apolipoprotein E (ApoE) COG 133 mimetic peptide in Swiss mice challenged with 5-fluorouracil (5-FU) and IEC-6 cell monolayers. Experiments were also performed in C57BL6J ApoE knockout mice to evaluate the effects of apoE peptide treatment.


The experimental groups were the following: unchallenged controls, mice challenged with 5-FU (450 mg/kg, IP) with or without the ApoE peptide (0.3, 1, and 3 μM, administered twice daily ip for 4 days ). Mice were sacrificed 3 days after the 5-FU challenge. Proximal small intestine samples were collected for molecular biology and histological processing. We perform ELISA and RT-PCR assays to target IL-1β, TNF-α, IL-10, iNOS, and myeloperoxidase (MPO) to assess intestinal inflammation.

Cell death and NF-κB assays were also performed in apoE knockout mice. In our in vitro models, IEC-6 cells were exposed to 1 mM 5-FU in medium without glutamine with or without the ApoE peptide (0.02, 0.2, 2, 5, 10, and 20 µM). We investigated the proliferation and migration of IEC-6 cells, 24 h after challenge with 5-FU. Furthermore, IEC-6 apoptotic cells were measured by Tunnel and flow cytometry. Equimolar doses of the ApoA-I (D4-F) peptide was also used in some experiments for comparative studies.


Villus attenuation and intense inflammatory infiltrate were observed in the 5-FU challenged group, findings that were partially ameliorated by the ApoE peptide. We found an increase in intestinal MPO and pro-inflammatory levels of IL-1β and TNF-α, and transcripts of TNF-α and iNOS, and reduction of IL-10 after treatment with 5-FU, each of which was partially abrogated by the peptide. Improvements in apoptosis and migration of IEC-6 cells were also found after treatment with ApoE and D-4F.


Taken together, these findings suggest that the novel ApoE COG 133 mimetic peptide may reduce 5-FU-induced intestinal changes and potentially benefit mucositis.

Keywords: mucositis, apolipoprotein E, 5-fluorouracil, inflammation, cytokines

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