中国肿瘤生物治疗杂志2025，Vol.32Issue(6)：570-578,9.DOI:10.3872/j.issn.1007-385x.2025.06.002
Id2通过PI3K/AKT通路调控Tcm细胞的代谢重编程抑制结肠癌细胞生长
Id2 regulates the metabolic reprogramming of Tcm cells through the PI3K/AKT pathway to inhibit colorectal cancer cell growth
摘要
Abstract
Objective:To investigate the role of inhibitor of differentiation 2(Id2)in inducing the generation of central memory T(Tcm)cells and enhancing the anti-tumor persistence of T cells.Methods:CD8+naïve T cells were sorted with magnetic beads and then co-cultured with carcinoembryonic antigen(CEA)-loaded dendritic cells(DCs).These cells were induced into effector T(Teff)or Tcm cells by interleukin-2(IL-2)or IL-7/15/21/23,respectively.The mRNA and protein expression of Id2 and Id3 in T cells were detected using qPCR and WB,respectively.Id2 gene in T cells was knocked down using lentivirus,and the T cell memory phenotype was analyzed by flow cytometry.The expression of PI3K/AKT pathway-related proteins was examined by WB.The extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)were assessed using a Seahorse extracellular flux analyzer.A zebrafish colorectal cancer HCT116 xenograft model was employed to analyze the anti-tumor differences between Teff and Tcm cells.The effect of Id2 gene knockdown in Tcm cells(Tcm-shId2)on the growth inhibition of secondary xenografts was also observed.Results:Tcm cells exhibited high expression of Id3 mRNA(P<0.05),whereas Teff cells showed high expression of Id2 mRNA(P<0.001).Tcm cells with Id2 knockdown(Tcm-shId2)were successfully constructed,showing significantly upregulated Id3 expression.Knockdown of Id2 promoted the formation of Tcm cell(P<0.05).Tcm-shId2 cells underwent metabolic reprogramming via the PI3K/AKT pathway,which effectively suppressed the growth of colorectal cancer xenografts in zebrafish and also produced significant inhibitory effects on secondary tumor growth(P<0.01).Conclusion:Id2 gene may regulate T cell metabolism through the PI3K/AKT signaling pathway,promoting the differentiation of CD8+T cells into Tcm cells and effectively inhibiting the growth of colorectal cancer xenografts.关键词
分化抑制因子2/中央记忆性T细胞/T细胞分化/PI3K/AKT信号通路/代谢重编程Key words
inhibitor of differentiation 2(Id2)/central memory T(Tcm)cell/T cell differentiation/PI3K/AKT signal pathway/metabolic reprogramming分类
医药卫生引用本文复制引用
刘枋,潘春丽,周智锋,陈淑萍,叶韵斌..Id2通过PI3K/AKT通路调控Tcm细胞的代谢重编程抑制结肠癌细胞生长[J].中国肿瘤生物治疗杂志,2025,32(6):570-578,9.基金项目
福建省卫生计生科研人才培养项目医学创新课题(No.2018-CX-9) （No.2018-CX-9）
福建省科技创新联合资金(No.2018Y9108) （No.2018Y9108）
福建省自然科学基金(No.2023J011247) （No.2023J011247）
福建省科技创新联合资金(No.2024Y9607) （No.2024Y9607）
