军事医学2026，Vol.50Issue(7)：489-497,9.DOI:10.7644/j.issn.1674-9960.2026-00030
环孢素A通过诱导铁死亡增强胰腺癌细胞的放疗敏感性
Cyclosporine A enhances the radiosensitivity of pancreatic cancer cells by inducing ferroptosis
摘要
Abstract
Objective To investigate the sensitizing effect of cyclosporine A(CsA)in combination with radiation therapy on pancreatic cancer cells(BxPC-3 and MIA PaCa-2)and explore the underlying mechanisms.Methods Network pharmacology was used to identify the common targets between CsA,ferroptosis,and radiosensitization for pancreatic cancer,followed by enrichment analysis and molecular docking predictions.In vitro experiments were performed using BxPC-3 and MIA PaCa-2 pancreatic cancer cell lines.Cells were divided into five groups:control,CsA alone,irradiation alone,CsA plus irradiation,and CsA plus irradiation plus Ferrostatin-1(Fer-1).The CCK-8 assay was used to assess the effect of CsA on cell viability and determine the optimal concentration for subsequent experiments.Cell survival and proliferative capacity were evaluated via trypan blue staining and clonogenic assays.Apoptosis was measured by flow cytometry,and lipid peroxidation levels were determined using the BODIPY 581/591 C11 probe.Real-time quantitative PCR(RT-qPCR)and Western blotting were used to analyze the expressions of ACSL4,SLC7A11,and GPX4 at both the mRNA and protein levels.Results Network pharmacology analysis suggested that CsA might regulate the ferroptosis pathway through the key target SLC7A11.In vitro experiments showed that CsA significantly reduced pancreatic cancer cell viability in a concentration-dependent manner compared to the control group,with a synergistic effect when combined with irradiation.Compared with the irradiation-alone group,the combination of CsA and irradiation significantly reduced cell viability,inhibited cell proliferation,decreased colony formation,and promoted apoptosis.These effects were partially reversed by the ferroptosis inhibitor Fer-1.Mechanistically,the combination of CsA with irradiation significantly induced lipid peroxidation,downregulated the expressions of SLC7A11 and GPX4,and upregulated the expression of ACSL4,all of which were reversed by Fer-1.Conclusion CsA enhances the radiosensitivity of pancreatic cancer cells by modulating the SLC7A11/GPX4/ACSL4 signaling axis to induce ferroptosis.This study provides evidence for clinical applications of CsA as a ferroptosis-inducing radiosensitizer in pancreatic cancer.关键词
环孢素A/胰腺癌/放射敏感性/铁死亡/放射治疗/网络药理学Key words
cyclosporine A/pancreatic cancer/radiosensitivity/ferroptosis/radiation therapy/network pharmacology分类
医药卫生引用本文复制引用
赵纪伟,申星,余祖胤,孙刚,彭疏篁,刘涵菲,王婧,纪奥强,陈怡,张瀚文,吴俊嶺,王淑芳..环孢素A通过诱导铁死亡增强胰腺癌细胞的放疗敏感性[J].军事医学,2026,50(7):489-497,9.基金项目
军队高层次科技创新人才工程学科拔尖人才培育项目(GCCRC-2024-002) （GCCRC-2024-002）
