1Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; 2Department of Radiation Oncology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
Abstract:Radiation-induced lung injury (RILI) is a common complication after radiotherapy for lung cancer and alternative thoracic malignant tumors, while ferroptosis is a regulated cell death triggered by iron-dependent membrane lipid peroxidation. In this article, the relationship between RILI and ferroptosis was investigated from oxidative damage induced by reactive oxygen species, antioxidant network and iron homeostasis regulated by nuclear factor erythroid 2-related factor 2(Nrf2) as well as transforming growth factor involved in the inflammatory response, aiming to mitigate or inhibit the occurrence of RILI through regulating ferroptosis, thereby improving clinical prognosis of patients undergoing radiotherapy.
Zheng Yuming,Jiang Mawei,Zheng Leizhen et al. Research progress on the association between radiation-induced lung injury and ferroptosis[J]. Chinese Journal of Radiation Oncology, 2021, 30(5): 527-530.
[1] The global cancer observatory. Cancer tomorrow. Explore the future of cancer burden[EB/OL][2020-04-30]. http://gco.iarc.fr/tomorrow/home. [2] Kong FM, Zhao J, Wang J, et al. Radiation dose effect in locally advanced non-small cell lung cancer[J]. J Thorac Dis, 2014, 6(4):336-347. DOI:10.3978/j.issn.2072-1439.2014.01.23. [3] Kong FM, Ten Haken RK, Schipper MJ, et al. High-dose radiation improved local tumor control and overall survival in patients with inoperable/unresectable non-small-cell lung cancer:long-term results of a radiation dose escalation study[J]. Int J Radiat Oncol Biol Phys, 2005, 63(2):324-333. DOI:10.1016/j.ijrobp.2005.02.010. [4] Farr KP, Khalil AA, Knap MM, et al. Development of radiation pneumopathy and generalised radiological changes after radiotherapy are independent negative prognostic factors for survival in non-small cell lung cancer patients[J]. Radiother Oncol, 2013, 107(3):382-388. DOI:10.1016/j.radonc.2013.04.024. [5] Schaue D, McBride WH. Opportunities and challenges of radiotherapy for treating cancer[J]. Nat Rev Clin Oncol, 2015, 12(9):527-540. DOI:10.1038/nrclinonc.2015.120. [6] Stauder MC, Macdonald OK, Olivier KR, et al. Early pulmonary toxicity following lung stereotactic body radiation therapy delivered in consecutive daily fractions[J]. Radiother Oncol, 2011, 99(2):166-171. DOI:10.1016/j.radonc.2011.04.002. [7] 任雪,阎英,徐莹,等. 放射性肺炎临床研究进展[J]. 创伤与急危重病医学, 2017, 5(5):309-313. DOI:10.16048/j.issn.2095-5561.2017.05.13. Ren X, Yan Y, Xu Y, et al. Clinical research progress in radiation pneumonitis[J]. Trauma Crit Care Med, 2017, 5(5):309-313. DOI:10.16048/j.issn.2095-5561.2017.05.13. [8] Ye LF, Chaudhary KR, Zandkarimi F, et al. Radiation-induced lipid peroxidation triggers ferroptosis and synergizes with ferroptosis inducers[J]. ACS Chem Biol, 2020, 15(2):469-484. DOI:10.1021/acschembio.9b00939. [9] Xie Y, Hou W, Song X, et al. Ferroptosis:process and function[J]. Cell Death Differ, 2016, 23(3):369-379. DOI:10.1038/cdd.2015.158. [10] Li X, Duan L, Yuan S, et al. Ferroptosis inhibitor alleviates radiation-induced lung fibrosis (RILF) via down-regulation of TGF-β1[J]. J Inflamm (Lond), 2019, 16:11. DOI:10.1186/s12950-019-0216-0. [11] Anuranjani, Bala M. Concerted action of Nrf2-ARE pathway, MRN complex, HMGB1 and inflammatory cytokines-implication in modification of radiation damage[J]. Redox Biol, 2014, 2:832-846. DOI:10.1016/j.redox.2014.02.008. [12] Sridharan DM, Asaithamby A, Bailey SM, et al. Understanding cancer development processes after HZE-particle exposure:roles of ROS, DNA damage repair and inflammation[J]. Radiat Res, 2015, 183(1):1-26. DOI:10.1667/RR13804.1. [13] 李成城,张秋宁,王小虎. 活性氧与放射性肺损伤的相关研究进展[J]. 辐射研究与辐射工艺学报, 2019, 37(6):1-7. DOI:10.11889/j.1000-3436.2019.rrj.37.060101. Li CC, Zhang QN, Wang XH. A review of the relationship of reactive oxygen species with radiation-induced lung injuries[J]. J Radiat Res Radiat Proc, 2019, 37(6):1-7. DOI:10.11889/j.1000-3436.2019.rrj.37.060101. [14] Spitz DR, Azzam EI, Li JJ, et al. Metabolic oxidation/reduction reactions and cellular responses to ionizing radiation:a unifying concept in stress response biology[J]. Cancer Metast Rev, 2004, 23(3-4):311-322. DOI:10.1023/B:CANC.0000031769.14728.bc. [15] Li X, Zhuang X, Qiao T. Role of ferroptosis in the process of acute radiation-induced lung injury in mice[J]. Biochem Biophys Res Commun, 2019, 519(2):240-245. DOI:10.1016/j.bbrc.2019.08.165. [16] Gong Y, Wang N, Liu N, et al. Lipid peroxidation and GPX4 inhibition are common causes for myofibroblast differentiation and ferroptosis[J]. DNA Cell Biol, 2019, 38(7):725-733. DOI:10.1089/dna.2018.4541. [17] Dinkova-Kostova AT, Kostov RV, Canning P. Keap1, the cysteine-based mammalian intracellular sensor for electrophiles and oxidants[J]. Arch Biochem Biophys, 2017, 617:84-93. DOI:10.1016/j.abb.2016.08.005. [18] Tian X, Wang F, Luo Y, et al. Protective role of nuclear factor-erythroid 2-related factor 2 against radiation-induced lung injury and inflammation[J]. Front Oncol, 2018, 8:542. DOI:10.3389/fonc.2018.00542. [19] Fan Z, Wirth AK, Chen D, et al. Nrf2-keap1 pathway promotes cell proliferation and diminishes ferroptosis[J]. Oncogenesis, 2017, 6(8):e371. DOI:10.1038/oncsis.2017.65. [20] Dodson M, Castro-Portuguez R, Zhang DD. NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis[J]. Redox Biol, 2019, 23:101107. DOI:10.1016/j.redox.2019.101107. [21] Kerins MJ, Ooi A. The roles of NRF2 in modulating cellular iron homeostasis[J]. Antioxid Redox Signal, 2018, 29(17):1756-1773. DOI:10.1089/ars.2017.7176. [22] Lim PJ, Duarte TL, Arezes J, et al. Nrf2 controls iron homeostasis in haemochromatosis and thalassaemia via Bmp6 and hepcidin[J]. Nat Metab, 2019, 1(5):519-531. DOI:10.1038/s42255-019-0063-6. [23] Sangiuolo F, Puxeddu E, Pezzuto G, et al. HFE gene variants and iron-induced oxygen radical generation in idiopathic pulmonary fibrosis[J]. Eur Respir J, 2015, 45(2):483-490. DOI:10.1183/09031936.00104814. [24] Zhang XH, Lou ZC, Wang AL, et al. Development of serum iron as a biological dosimeter in mice[J]. Radiat Res, 2013, 179(6):684-689. DOI:10.1667/RR3142.1. [25] Budagov RS, Ashurov AA,ZaǐchikVE. Blood trace elements as an indicator of the degree of severity in radiation lesions[J]. Radiats Biol Radioecol, 1994, 34(1):49-54. [26] Li X, Xu G, Qiao T, et al. Effects of CpG Oligodeoxynucleotide 1826 on transforming growth factor-beta 1 and radiation-induced pulmonary fibrosis in mice[J]. J Inflamm (Lond), 2016, 13:16. DOI:10.1186/s12950-016-0125-4. [27] Anscher MS, Murase T, Prescott DM, et al. Changes in plasma TGF beta levels during pulmonary radiotherapy as a predictor of the risk of developing radiation pneumonitis[J]. Int J Radiat Oncol Biol Phys, 1994, 30(3):671-676. DOI:10.1016/0360-3016(92)90954-g. [28] 陈志远,董卓,魏威,等. TGF-β1对放射性肺纤维化作用的研究进展[J]. 辐射防护, 2018, 38(2):171-175. Chen ZY, Dong Z, Wei W, et al. Research progress of TGF-β1 on radiation-induced pulmonary fibrosis[J]. Radiat Prot, 2018, 38(2):171-175. [29] Kim JY, Kim YS, Kim YK, et al. The TGF-beta1 dynamics during radiation therapy and its correlation to symptomatic radiation pneumonitis in lung cancer patients[J]. Radiat Oncol, 2009, 4:59. DOI:10.1186/1748-717x-4-59. [30] Wang S, Campbell J, Stenmark MH, et al. Plasma levels of IL-8 and TGF-β1 predict radiation-induced lung toxicity in non-small cell lung cancer:a validation study[J]. Int J Radiat Oncol Biol Phys, 2017, 98(3):615-621. DOI:10.1016/j.ijrobp.2017.03.011. [31] Zhao L, Sheldon K, Chen M, et al. The predictive role of plasma TGF-β1 during radiation therapy for radiation-induced lung toxicity deserves further study in patients with non-small cell lung cancer[J]. Lung Cancer, 2008, 59(2):232-239. DOI:10.1016/j.lungcan.2007.08.010. [32] Fu XL, Huang H, Bentel G, et al. Predicting the risk of symptomatic radiation-induced lung injury using both the physical and biologic parameters V (30) and transforming growth factor beta[J]. Int J Radiat Oncol Biol Phys, 2001, 50(4):899-908. DOI:10.1016/s0360-3016(01)01524-3. [33] Meng XM, Nikolic-Paterson DJ, Lan HY. TGF-beta:the master regulator of fibrosis[J]. Nat Rev Nephrol, 2016, 12(6):325-338. DOI:10.1038/nrneph.2016.48. [34] Anscher MS, Thrasher B, Zgonjanin L, et al. Small molecular inhibitor of transforming growth factor-beta protects against development of radiation-induced lung injury[J]. Int J Radiat Oncol Biol Phys, 2008, 71(3):829-837. DOI:10.1016/j.ijrobp.2008.02.046. [35] Rübe CE, Palm J, Erren M, et al. Cytokine plasma levels:reliable predictors for radiation pneumonitis?[J/OL]. PLoS One, 2008, 3(8):e2898. DOI:10.1371/journal.pone.0002898. [36] Novakova-Jiresova A, Van Gameren MM, Coppes RP, et al. Transforming growth factor-β plasma dynamics and post-irradiation lung injury in lung cancer patients[J]. Radiother Oncol, 2004, 71(2):183-189. DOI:10.1016/j.radonc.2004.01.019. [37] Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis:an iron-dependent form of nonapoptotic cell death[J]. Cell, 2012, 149(5):1060-1072. DOI:10.1016/j.cell.2012.03.042. [38] Johnston CJ, Hernady E, Reed C, et al. Early alterations in cytokine expression in adult compared to developing lung in mice after radiation exposure[J]. Radiat Res, 2010, 173(4):522-535. DOI:10.1667/RR1882.1.