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As an important part of comprehensive tumor treatment, dual-protein (DP) nutritional intervention is attracting more and more attention. Methods: This study preliminarily evaluated the regulatory effects of DP intervention on colorectal cells of CT26 tumor-bearing mice, examining the dosage and administration methods of DP, as well as the anti-tumor effects of FU alone or in combination with DP. Results: The results showed that low- and medium-dose DP numerically increased spleen index and showed trends toward alleviating FU-induced thymic atrophy, splenic damage, nephrotoxicity, and myocardial injury. It also partly mitigated muscle wasting, prevented FU-induced shortening of the colorectal tract, and reduced intestinal injury. In addition, DP was associated with increased lymphocyte, monocyte, and platelet counts and decreased granulocytes, suggesting possible alleviation of chemotherapy-induced bone marrow suppression and a potential effect on hematopoietic function. Flow cytometry results indicated possible effects of DP on CD4+ T and CD8+ T cell proliferation or apoptosis, modulation of effector and memory phenotypes, reduced splenic neutrophil levels, balanced B cell function, and maintained natural killer cell activity. In addition, DP intervention also showed trends toward regulating hepatic lipid metabolism and partially alleviating FU-induced dyslipidemia and muscle damage. In addition, DP and FU could increase IL-2, IL-10, GM-CSF and IFN-\u03b3 and decrease IL-6 and TNF-\u03b1. Conclusions: In conclusion, a moderate dose (0.67 g\/kg) of DP had the most favorable trends, and the pre-intervention mode was more effective. This study also provided exploratory data on the potential of DP in reducing chemotherapy-related toxicity. These findings will provide preliminary scientific support for nutritional therapy in colorectal cancer patients, as well as for the research, development, and application of dual-protein foods for special medical purposes.<\/jats:p>","DOI":"10.3390\/nu18111663","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T13:12:08Z","timestamp":1779455528000},"page":"1663","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual-Protein Intervention in CT26 Tumor-Bearing Mice: A Preliminary Evaluation of Its Effects on Anti-Tumor Efficacy of 5-Fluorouracil and Immune Responses"],"prefix":"10.3390","volume":"18","author":[{"given":"Duo","family":"Feng","sequence":"first","affiliation":[{"name":"Institute of Food and Nutrition Development, Ministry of Agriculture and Rural Affairs, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjie","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Food and Nutrition Development, Ministry of Agriculture and Rural Affairs, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5603-8495","authenticated-orcid":false,"given":"Di","family":"Han","sequence":"additional","affiliation":[{"name":"Institute of Food and Nutrition Development, Ministry of Agriculture and Rural Affairs, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghan","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Food and Nutrition Development, Ministry of Agriculture and Rural Affairs, Beijing 100081, China"},{"name":"Special Food Research Institute, Qingdao Agricultural University, Qingdao 266109, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Man","sequence":"additional","affiliation":[{"name":"Institute of Food and Nutrition Development, Ministry of Agriculture and Rural Affairs, Beijing 100081, China"},{"name":"Special Food Research Institute, Qingdao Agricultural University, Qingdao 266109, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Food and Nutrition Development, Ministry of Agriculture and Rural Affairs, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Food and Nutrition Development, Ministry of Agriculture and Rural Affairs, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqi","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Food and Nutrition Development, Ministry of Agriculture and Rural Affairs, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Fan","sequence":"additional","affiliation":[{"name":"Institute of Food and Nutrition Development, Ministry of Agriculture and Rural Affairs, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Food and Nutrition Development, Ministry of Agriculture and Rural Affairs, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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