肿瘤预防与治疗2026，Vol.39Issue(7)：524-534,11.DOI:10.3969/j.issn.1674-0904.2026.07.002
基于SLC7A11/GPX4通路研究阿帕替尼联合卡瑞利珠促进结直肠癌铁死亡的机制
Apatinib Combined with Camrelizumab in Promoting Ferroptosis for Colorectal Cancer Based on the SLC7A11/GPX4 Pathway
摘要
Abstract
Objective:To investigate the anti-tumor effects of apatinib combined with camrelizumab in colorectal cancer,and to determine whether this combination induces ferroptosis to enhance CD8+T cell-mediated anti-tumor immunity.Meth-ods:In vitro co-culture models of human colorectal cancer HCT116,SW480 cells and CD8+T cells were established.The models were assigned to control group,apatinib group,camrelizumab group and combination therapy group.We measured cell viability,colony formation rate,lactate dehydrogenase(LDH)release,levels of immune effector molecules(IFN-γ,TNF-α,Granzyme B,and Perforin),and ferroptosis-related markers(Fe2+,MDA,GSH,SOD,ROS,GPX4,and SLC7A11).The ferroptosis inhibitor Ferrostatin-1(Fer-1)was used to validate the underlying mechanism.Western blot was employed to analyze T cell infiltration and programmed cell death-ligand 1 expression.Results:Compared with monother-apy,the combination therapy significantly inhibited tumor cell viability and colony formation,promoted CD8+T cell infiltration and immune effector molecule secretion,and increased LDH release(P<0.01).Meanwhile,Fe2+,MDA and ROS levels increased,GSH levels declined,and the expression of GPX4 and SLC7A11 was down-regulated in the combination therapy group.Fer-1 partially reversed the above effects.Conclusion:Apatinib combined with camrelizumab may enhance T cell-mediated anti-tumor immune responses by inducing ferroptosis in tumor cells.This combination strategy provides new insights for immunotherapy of colorectal cancer.关键词
结直肠癌/阿帕替尼/卡瑞利珠单抗/铁死亡/PD-L1/免疫治疗Key words
Colorectal cancer/Apatinib/Camrelizumab/Ferroptosis/PD-L1/Immunotherapy分类
生物科学引用本文复制引用
王译,侯静静,谷雨,王岩,唐琳琳,毕文超..基于SLC7A11/GPX4通路研究阿帕替尼联合卡瑞利珠促进结直肠癌铁死亡的机制[J].肿瘤预防与治疗,2026,39(7):524-534,11.基金项目
This study was supported by grants from Shandong Medical Association(No.YXH2022ZX02055).山东省医学会临床科研基金-齐鲁专项(编号:YXH2022ZX02055) （No.YXH2022ZX02055）
