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(Landmark Ed)"],"abstract":"<jats:p>Background:Chemoresistance to oxaliplatin (OXA) in colorectal cancer (CRC) remains a major cause of treatment failure. This study investigated whether Huaier polysaccharide (HP) could reverse OXA resistance and explored the underlying mechanisms.Methods:Cell viability and proliferation were assessed using the Cell Counting Kit-8 (CCK-8) assay and colony formation assays, respectively. Protein expression was analyzed by Western blotting. Ferroptosis was evaluated using a lipid peroxidation probe (BDP 581\/591 C11), FerroOrange, a reactive oxygen species (ROS) assay kit, and a total glutathione detection kit. Ultrastructural changes were observed using transmission electron microscopy. Nuclear and cytoplasmic protein extraction and immunofluorescence were used to examine nuclear factor erythroid 2-related factor 2 (Nrf2) expression.Results:Combined treatment with OXA and HP significantly suppressed cell viability and proliferation by inhibiting the Nrf2\/solute carrier family 7 member 11 (SLC7A11)\/glutathione peroxidase 4 (GPX4) pathway, thereby inducing ferroptosis. In addition, HP reduced P-glycoprotein expression and enhanced sensitivity to OXA.Conclusions:These findings demonstrate that Huaier overcomes OXA resistance in CRC cells by promoting ferroptosis through suppression of the Nrf2\/SLC7A11\/GPX4 signaling pathway in vitro.<\/jats:p>","DOI":"10.31083\/fbl47735","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:50:51Z","timestamp":1783421451000},"source":"Crossref","is-referenced-by-count":0,"title":["Huaier Sensitizes Oxaliplatin-Resistant Colorectal Cancer to Oxaliplatin by Reducing P-Glycoprotein and Inducing Nrf2\/SLC7A11\/GPX4-Dependent Ferroptosis"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6287-0263","authenticated-orcid":true,"given":"Guizhen","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, Chengde Medical University, 067000 Chengde, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6819-8484","authenticated-orcid":true,"given":"Yanan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Chengde Medical University, 067000 Chengde, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6614-2680","authenticated-orcid":true,"given":"Hairu","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Chengde Medical University, 067000 Chengde, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0545-0436","authenticated-orcid":true,"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology Chengde, Affiliated Hospital of Chengde Medical University, 067000 Chengde, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3705-3432","authenticated-orcid":true,"given":"Zhiping","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Chengde Medical University, 067000 Chengde, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0546-7526","authenticated-orcid":true,"given":"Jining","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Chengde Medical University, 067000 Chengde, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. 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