
浏览全部资源
扫码关注微信
1.中国医科大学附属盛京医院放射治疗室,沈阳 110022
2.中国医科大学附属盛京医院肿瘤多组学研究创新实验室, 本溪 117004
3.中国医科大学附属盛京医院放射科,沈阳 110022
关宇廷,Email:280993918@qq.com,研究方向:放射医学、肿瘤学。
石驰宇,Email:2245894819@qq.com。
收稿:2025-07-24,
修回:2025-10-23,
录用:2025-11-13,
纸质出版:2026-04-28
移动端阅览
关宇廷,陈熹铭,石驰宇.IL-8在非小细胞肺癌放疗耐受性中的作用及潜在靶向策略[J].重庆医科大学学报,2026,51(4):516-521.
Guan Yuting,Chen Ximing,Shi Chiyu.Role of interleukin-8 in radiotherapy resistance of non-small cell lung cancer and potential strategies for targeted therapy[J].Journal of Chongqing Medical University,2026,51(4):516-521.
关宇廷,陈熹铭,石驰宇.IL-8在非小细胞肺癌放疗耐受性中的作用及潜在靶向策略[J].重庆医科大学学报,2026,51(4):516-521. DOI: 10.13406/j.cnki.cyxb.004010.
Guan Yuting,Chen Ximing,Shi Chiyu.Role of interleukin-8 in radiotherapy resistance of non-small cell lung cancer and potential strategies for targeted therapy[J].Journal of Chongqing Medical University,2026,51(4):516-521. DOI: 10.13406/j.cnki.cyxb.004010.
目的
2
探讨白细胞介素-8(interleukin-8,IL-8)通过调控FAS细胞表面死亡受体(FAS cell surface death receptor,FAS)/FAS细胞表面死亡配体(FAS cell surface death receptor ligand,FASL)通路在非小细胞肺癌(non-small cell lung cancer,NSCLC)放疗耐受性中的作用,并评估靶向IL-8信号通路作为改善放疗效果的潜在策略。
方法
2
利用酶联免疫吸附测定法检测放疗前后NSCLC患者血清中IL-8和可溶性FAS配体(soluble FAS ligand,sFASL)水平的变化,并使用IL-8受体抑制剂Repertaxin观察NSCLC细胞对放疗的敏感性变化,分析IL-8在FAS/FASL通路中的调控作用。
结果
2
放疗后患者血清中IL-8和sFASL水平均发生明显变化。放疗前3 d血清IL-8中位数为6.60 pg/mL,放疗后8周升至8.73 pg/mL,差异有统计学意义(
P
=0.033),提示IL-8水平在放疗后明显升高且持续时间较长。sFASL方面,放疗前3 d血清中位数为32.0 pg/mL,放疗后8周为161.4 pg/mL,差异
有统计学意义(
P
<
0.001)。提示IL-8通过抑制FAS/FASL通路降低肿瘤细胞凋亡,削弱放疗效果。Repertaxin处理后,NSCLC细胞在放疗48 h的凋亡率明显高于未处理组,表明阻断IL-8信号通路可增强肿瘤对放疗的敏感性。
结论
2
IL-8通过调控FAS/FASL通路促进NSCLC放疗耐受,靶向IL-8或CXC趋化因子受体1(C-X-C motif chemokine receptor 1,CXCR1)有望成为克服耐受、提高放疗疗效的新策略。
Objective
2
To investigate the role of interleukin-8(IL-8) in radiotherapy resistance of non-small cell lung cancer (NSCLC) by regulating the FAS(FAS cell surface death receptor)/FASL(FAS ligand) pathway,and to assess the effect of IL-8 signaling pathway-targeted therapy in improving the efficacy of radiotherapy.
Methods
2
ELISA was used to measure the changes in the serum levels of IL-8 and soluble FAS ligand(sFASL) in NSCLC patients before and after radiotherapy. The IL-8 receptor inhibitor Repertaxin was used to observe the change in the sensitivity of NSCLC cells to radiotherapy,and the regulatory role of IL-8 in the FAS/FASL pathway was analyzed.
Results
2
After radiotherapy,the patients showed significant changes in the serum levels of IL-8 and sFASL. The median serum level of IL-8 increased from 6.60 pg/mL on day 3 before radiotherapy to 8.73 pg/mL at 8 weeks after radiotherapy(
P
=0.033),suggesting that there was a constant and significant increase in IL-8 level after radiotherapy. The median serum level of sFASL increased from 32.0 pg/mL on day 3 before radiotherapy to 161.4 pg/mL at 8 weeks after radiotherapy(
P
<
0.001). IL-8 reduced tumor cell apoptosis and weakened the efficacy of radiotherapy by inhibiting the FAS/FASL pathway. The NSCLC cells treated with Repertaxin had a significantly higher apoptosis rate at 48 hours after radiotherapy than those without treatment,suggesting that blocking the IL-8 signaling pathway could enhance the sensitivity of tumor to radiotherapy.
Conclusion
2
IL-8 alleviates radiotherapy resistance in NSCLC by regulating the FAS/FASL pathway,and targeting IL-8 or C-X-C motif chemokine receptor 1 may become a new strategy to overcome resistance and enhance the efficacy of radiotherapy.
Megyesfalvi Z , Gay CM , Popper H , et al . Clinical insights into small cell lung cancer: Tumor heterogeneity,diagnosis,therapy,and future directions [J ] . CA Cancer J Clin , 2023 , 73 ( 6 ): 620 - 652 .
Yoshida D , Kusunoki T , Takayama Y , et al . Comparison of dose distribution between VMAT-SBRT and scanning carbon-ion radiotherapy for early-stage NSCLC [J ] . Anticancer Res , 2021 , 41 ( 9 ): 4571 - 4575 .
郑保珍 , 汪雅芬 , 董智慧 , 等 . 放疗联合免疫治疗在局部晚期非小细胞肺癌中的疗效及安全性分析 [J ] . 系统医学 , 2024 , 9 ( 16 ): 143 - 146,158 .
Zheng BZ , Wang YF , Dong ZH , et al . Analysis of the efficacy and safety of radiotherapy combined with immunotherapy in locally advanced non-small cell lung cancer [J ] . Syst Med , 2024 , 9 ( 16 ): 143 - 146,158 .
谢馥霞 , 李梦丹 , 王小会 , 等 . 18F-FDG PET/CT联合外周血炎症因子评估晚期非小细胞肺癌免疫治疗疗效的价值 [J ] . 现代肿瘤医学 , 2023 , 31 ( 17 ): 3209 - 3215 .
Xie FX , Li MD , Wang XH , et al . Value of 18F-FDG PET/CT combined with inflammatory factors in peripheral blood in evaluating the efficacy of immunotherapy for advanced NSCLC [J ] . J Mod Oncol , 2023 , 31 ( 17 ): 3209 - 3215 .
Chen Y , Gao M , Huang ZQ , et al . SBRT combined with PD-1/PD-L1 inhibitors in NSCLC treatment: a focus on the mechanisms,advances,and future challenges [J ] . J Hematol Oncol , 2020 , 13 ( 1 ): 105 .
Brada M , Forbes H , Ashley S , et al . Improving outcomes in NSCLC: optimum dose fractionation in radical radiotherapy matters [J ] . J Thorac Oncol , 2022 , 17 ( 4 ): 532 - 543 .
Yang JM , Kumar A , Vilgelm AE , et al . Loss of CXCR4 in myeloid cells enhances antitumor immunity and reduces melanoma growth through NK cell and FASL mechanisms [J ] . Cancer Immunol Res , 2018 , 6 ( 10 ): 1186 - 1198 .
Sato Y , Yoshino H , Tsuruga E , et al . Fas ligand enhances apoptosis of human lung cancer cells cotreated with RIG-I-like receptor agonist and radiation [J ] . Curr Cancer Drug Targets , 2020 , 20 ( 5 ): 372 - 381 .
Ginestier C , Liu SL , Diebel ME , et al . CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts [J ] . J Clin Invest , 2010 , 120 ( 2 ): 485 - 497 .
Corrò C , Healy ME , Engler S , et al . IL-8 and CXCR1 expression is associated with cancer stem cell-like properties of clear cell renal cancer [J ] . J Pathol , 2019 , 248 ( 3 ): 377 - 389 .
Kumar A , Shalmanova L , Hammad A , et al . Induction of IL-8(CXCL8) and MCP-1(CCL2) with oxidative stress and its inhibition with N-acetyl cysteine (NAC) in cell culture model using HK-2 cell [J ] . Transpl Immunol , 2016 , 35 : 40 - 46 .
Mosleh-Shirazi MA , Kazempour S , Fardid R , et al . Intra-fractional dose rate effect in continuous and interrupted irradiation of the MCF-7 cell line: Possible radiobiological implications for breath-hold techniques in breast radiotherapy [J ] . J Cancer Res Ther , 2024 , 20 ( 3 ): 863 - 868 .
Liu K , Zhao XK , Gu J , et al . Eff ects of 12 C6+ heavy ion beam irradiation on the p53 signaling pathway in HepG2 liver cancer cells [J ] . Acta Biochim Biophys Sin , 2017 , 49 ( 11 ): 989 - 998 .
Singh S , Wu S , Varney M , et al . CXCR1 and CXCR2 silencing modulates CXCL8-dependent endothelial cell proliferation,migration and capillary-like structure formation [J ] . Microvasc Res , 2011 , 82 ( 3 ): 318 - 325 .
Koshkina N , Yang YZ , Kleinerman ES . The fas/FasL signaling pathway: its role in the metastatic process and as a target for treating osteosarcoma lung metastases [J ] . Adv Exp Med Biol , 2020 , 1258 : 177 - 187 .
Singh JK , Simões BM , Howell SJ , et al . Recent advances reveal IL-8 signaling as a potential key to targeting breast cancer stem cells [J ] . Breast Cancer Res , 2013 , 15 ( 4 ): 210 .
Brandolini L , Cristiano L , Fidoamore A , et al . Targeting CXCR1 on breast cancer stem cells:signaling pathways and clinical application modelling [J ] . Oncotarget , 2015 , 6 ( 41 ): 43375 - 43394 .
Matsumoto N , Imamura R , Suda T . Caspase-8- and JNK-dependent AP-1 activation is required for Fas ligand-induced IL-8 production [J ] . FEBS J , 2007 , 274 ( 9 ): 2376 - 2384 .
Ariyoshi K , Miura T , Kasai K , et al . Radiation-induced bystander effect is mediated by mitochondrial DNA in exosome-like vesicles [J ] . Sci Rep , 2019 , 9 ( 1 ): 9103 .
Tang HY , Cai LW , He XY , et al . Radiation-induced bystander effect and its clinical implications [J ] . Front Oncol , 2023 , 13 : 1124412 .
Wang R , Zhou TY , Liu W , et al . Molecular mechanism of bystander effects and related abscopal/cohort effects in cancer therapy [J ] . Oncotarget , 2018 , 9 ( 26 ): 18637 - 18647 .
Zhang C , Liang ZZ , Ma SM , et al . Radiotherapy and cytokine storm: risk and mechanism [J ] . Front Oncol , 2021 , 11 : 670464 .
Najafi M , Fardid R , Hadadi G , et al . The mechanisms of radiation-induced bystander effect [J ] . J Biomed Phys Eng , 2014 , 4 ( 4 ): 163 - 172 .
Kurenova E , Xu LH , Yang XH , et al . Focal adhesion kinase suppresses apoptosis by binding to the death domain of receptor-interacting protein [J ] . Mol Cell Biol , 2004 , 24 ( 10 ): 4361 - 4371 .
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621