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OA

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.