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Song F, Che J, Li H, Zhu G, Huang M, Xu D. Iodine-125 radiation inhibits epithelial-mesenchymal transition in lung cancer cells by blocking TGF-β1/Smad3/Snai1 signaling. Int J Radiat Res 2025; 23 (3) :751-756 URL: http://ijrr.com/article-1-6668-en.html
Department of Medical Laboratory, Pingbian County People's Hospital, Pingbian 661200, Yunnan, China & Department of Medical Laboratory, Pingbian County People's Hospital, Pingbian 661200, Yunnan, China , 632533054@qq.com
Abstract: (222 Views)
Background: Iodine-125 (125I) brachytherapy is an effective strategy for treating human tumors. The current study aimed to discover the mechanisms underlying the therapeutic action of 125I radiation in lung cancer, with a focus on its impact on the epithelial-mesenchymal transition (EMT). Materials and Methods: A549 cells, a human lung adenocarcinoma cell line, were treated with transforming growth factor β1 (TGF-β1) and/or 125I (control, TGF-β1, 125I, and TGF-β1 + 125I groups) to evaluate the effects of 125I on TGF-β1-induced EMT. After treatment, the viability of A549 cells was detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of E-cadherin, N-cadherin, Vimentin, Smad3, and Snai1 markers and pathway molecules was measured. Results: 125I radiation inhibited the viability of A549 cells, both with and without TGF-β1 treatment. TGF-β1 intervention promoted the EMT of A549 cells, as demonstrated by the morphological transition from a polygonal shape to a spindle shape, reduced E-cadherin levels, and elevated Vimentin and N-cadherin expression. Notably, TGF-β1-activated EMT was significantly weakened by 125I radiation. Moreover, 125I radiation reversed TGF-β1-induced upregulation of Smad3 and Snai1 in A549 cells. Conclusion: 125I radiation suppresses the EMT by blocking TGF-β1/Smad3/Snai1 signaling, contributing to the treatment of lung cancer.
References
1. 1. Thai AA, Solomon BJ, Sequist LV, Gainor JF, Heist RS (2021) Lung cancer. Lancet (London, England), 398(10299): 535-54. [ DOI:10.1016/S0140-6736(21)00312-3] 2. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of incidence and mortality worldwide for 36 cancers in 185 coun tries. CA Cancer J Clin, 71(3): 209-49. [ DOI:10.3322/caac.21660] 3. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a Cancer Journal for Clinicians, 74(3): 229-263. [ DOI:10.3322/caac.21834] 4. Schabath MB and Cote ML (2019) Cancer Progress and Priorities: Lung Cancer. Cancer Epidemiol Biomarkers Prev, 28(10): 1563-79. [ DOI:10.1158/1055-9965.EPI-19-0221] 5. Corrales L, Rosell R, Cardona AF, Martin C, Zatarain-Barron ZL, Ar rieta O (2020) Lung cancer in never smokers: The role of different risk factors other than tobacco smoking. Crit Rev Oncol Hematol, 148: 102895. [ DOI:10.1016/j.critrevonc.2020.102895] 6. Xue T, Zhao X, Zhao K, Lu Y, Yao J, Ji X (2022) Immunotherapy for lung cancer: Focusing on chimeric antigen receptor (CAR)-T cell therapy. Curr Probl Cancer, 46(1): 100791. [ DOI:10.1016/j.currproblcancer.2021.100791] 7. Alexander M, Kim SY, Cheng H (2020) Update 2020: Management of non-small cell lung cancer. Lung, 198(6): 897-907. [ DOI:10.1007/s00408-020-00407-5] 8. Denisenko TV, Budkevich IN, Zhivotovsky B (2018) Cell death-based treatment of lung adenocarcinoma. Cell Death Dis, 9(2): 117. [ DOI:10.1038/s41419-017-0063-y] 9. Herbst RS, Morgensztern D, Boshoff C (2018) The biology and man agement of non-small cell lung cancer. Nature, 553(7689): 446-54. [ DOI:10.1038/nature25183] 10. Otter SJ, Stewart AJ, Devlin PM (2019) Modern Brachytherapy. He matol Oncol Clin North Am, 33(6): 1011-25. [ DOI:10.1016/j.hoc.2019.08.011] 11. Deng X, Wu H, Gao F, Su Y, Li Q, Liu S, et al. (2017) Brachytherapy in the treatment of breast cancer. Int J Clin Oncol, 22(4): 641-50. [ DOI:10.1007/s10147-017-1155-5] 12. Takeshita A, Shimamoto H, Uchimoto Y, Tsujimoto T, Miyamoto T, Kreiborg S, et al. (2023) High-dose-rate mold brachytherapy for mandibular gingival squamous cell carcinoma in outpatient setting- Initial case report. International Journal of Radiation Research, 21(4): 849-53. [ DOI:10.61186/ijrr.21.4.849] 13. Li Y, Pang F, Cai H, Li L (2022) Intratumoral injection of radioactive Astatine (211At) microspheres for the treatment of tumors. Inter national Journal of Radiation Research, 20(4): 793-8. 14. Muñoz Arango E, Pickler A, Mantuano A, Salata C, de Almeida CE (2020) Feasibility study of the Fricke chemical dosimeter as an in dependent dosimetric system for the small animal radiation re search platform (SARRP). Physica Medica, 71: 168-75. [ DOI:10.1016/j.ejmp.2020.03.006] 15. Kaliki S and Shields CL (2017) Uveal melanoma: relatively rare but deadly cancer. Eye (Lond), 31(2): 241-57. [ DOI:10.1038/eye.2016.275] 16. Gao H, Wang Y, Du C, Li X, Liu K, Xue H, et al. (2022) Study on the factors affecting the dose error of using I-125 seeds in the treat ment of prostate cancer using the Monte Carlo method. Interna tional Journal of Radiation Research, 20(4): 857-64. 17. Ghahramani MR, Asgharizadeh F, Assadi MR, Ahmadi SJ, Moradi K (2012) Effects of different carriers for adsorption of I-125 on brachytherapy sources. International Journal of Radiation Re search, 10(2): 105-7. 18. Yu H, Zhang H, Gao Z, Liu X, Zhang L, Di X, et al. (2022) (125)I Seed brachytherapy for refractory loco-regional recurrence of non-anaplastic thyroid cancer. Frontiers in Oncology, 12: 773708. [ DOI:10.3389/fonc.2022.773708] 19. Huang S, Cao Y, Wang R, Liu H, Wang T, Yang S (2023) Feasibility of 125I brachytherapy combined with arterial infusion chemotherapy in patients with advanced pancreatic cancer. Medicine, 102(44): e35033. [ DOI:10.1097/MD.0000000000035033] 20. Yao X, Lu S, Feng C, Suo R, Li H, Zhang Y, et al. (2022) Tumor oxy genation nanoliposome synergistic hypoxia-inducible-factor-1 in hibitor enhanced Iodine-125 seed brachytherapy for esophageal cancer. Biomaterials, 289: 121801. [ DOI:10.1016/j.biomaterials.2022.121801] 21. Wang Y, Li F, Hu Y, Sun Y, Tian C, Cao Y, et al. (2023) Clinical out comes of intra-arterial chemotherapy combined with iodine-125 seed brachytherapy in the treatment of malignant superior vena cava syndrome caused by small cell lung cancer. Cancer Radiother apie, 27(4): 312-8. [ DOI:10.1016/j.canrad.2023.01.008] 22. Yang L, Wang C, Zhang W, Liu S, Xuan T, Jiang H, et al. (2022) Iodine-125 brachytherapy treatment for newly diagnosed brain metasta sis in non-small cell lung cancer: A biocentric analysis. Front Oncol, 12: 1005876. [ DOI:10.3389/fonc.2022.1005876] 23. Zhang W, Li J, Li R, Zhang Y, Han M, Ma W (2018) Efficacy and safe ty of iodine-125 radioactive seeds brachytherapy for advanced non-small cell lung cancer-A meta-analysis. Brachytherapy, 17(2): 439-48. [ DOI:10.1016/j.brachy.2017.11.015] 24. Hong J, Shi YB, Fu YF, Yang LL (2022) Iodine-125 seeds insertion with trans-arterial chemical infusion for advanced lung cancer: a meta-analysis. J Contemp Brachytherapy, 14(4): 403-10. [ DOI:10.5114/jcb.2022.118117] 25. Lamouille S, Xu J, Derynck R (2014) Molecular mechanisms of epi thelial-mesenchymal transition. Nat Rev Mol Cell Biol, 15(3): 178-96. [ DOI:10.1038/nrm3758] 26. Dongre A and Weinberg RA (2019) New insights into the mecha nisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol, 20(2): 69-84. [ DOI:10.1038/s41580-018-0080-4] 27. Debnath P, Huirem RS, Dutta P, Palchaudhuri S (2022) Epithelial-mesenchymal transition and its transcription factors. Biosci Rep, 42(1): BSR20211754. [ DOI:10.1042/BSR20211754] 28. Xu J, Lamouille S, Derynck R (2009) TGF-beta-induced epithelial to mesenchymal transition. Cell Res, 19(2): 156-72. [ DOI:10.1038/cr.2009.5] 29. Yuan R, Fan Q, Liang X, Han S, He J, Wang QQ, et al. (2022) Cucur bitacin B inhibits TGF-beta1-induced epithelial-mesenchymal tran sition (EMT) in NSCLC through regulating ROS and PI3K/Akt/mTOR pathways. Chin Med, 17(1): 24. [ DOI:10.1186/s13020-022-00581-z] 30. Jeong JH, Jang HJ, Kwak S, Sung GJ, Park SH, Song JH, et al. (2019) Novel TGF-beta1 inhibitor antagonizes TGF-beta1-induced epitheli al-mesenchymal transition in human A549 lung cancer cells. J Cell Biochem, 120(1): 977-87. [ DOI:10.1002/jcb.27460] 31. Kim J and Hwan Kim S (2013) CK2 inhibitor CX-4945 blocks TGF-β1-induced epithelial-to-mesenchymal transition in A549 human lung adenocarcinoma cells. PloS One, 8(9): e74342. [ DOI:10.1371/journal.pone.0074342] 32. Amiri A, Pourhanifeh MH, Mirzaei HR, Nahand JS, Moghoofei M, Sahebnasagh R, et al. (2021) Exosomes and lung cancer: roles in pathophysiology, diagnosis and therapeutic applications. Curr Med Chem, 28(2): 308-28. [ DOI:10.2174/1875533XMTA0tMjEF3] 33. Qiu B, Jiang P, Ji Z, Huo X, Sun H, Wang J (2021) Brachytherapy for lung cancer. Brachytherapy, 20(2): 454-66. [ DOI:10.1016/j.brachy.2020.11.009] 34. Du B and Shim JS (2016) Targeting Epithelial-mesenchymal transi tion (EMT) to overcome drug resistance in cancer. Molecules, 21(7): 965. [ DOI:10.3390/molecules21070965] 35. Roche J (2018) The epithelial-to-mesenchymal transition in cancer. Cancers (Basel), 10(2): 52. [ DOI:10.3390/cancers10020052] 36. Zhang Y and Weinberg RA (2018) Epithelial-to-mesenchymal tran sition in cancer: complexity and opportunities. Front Med, 12(4): 361-73. [ DOI:10.1007/s11684-018-0656-6] 37. Song L, Li XX, Liu XY, Wang Z, Yu Y, Shi M, et al. (2020) EFEMP2 Suppresses the invasion of lung cancer cells by inhibiting epithelial-mesenchymal transition (EMT) and down-regulating MMPs. Onco Targets Ther, 13: 1375-96. [ DOI:10.2147/OTT.S236111] 38. Chen J, Tong W, Liao M, Chen D (2020) Inhibition of arachidonate lipoxygenase12 targets lung cancer through inhibiting EMT and suppressing RhoA and NF-kappaB activity. Biochem Biophys Res Commun, 524(4): 803-9. [ DOI:10.1016/j.bbrc.2020.01.166] 39. Zhu N, Zhang XJ, Zou H, Zhang YY, Xia JW, Zhang P, et al. (2021) PTPL1 suppresses lung cancer cell migration via inhibiting TGF-beta1-induced activation of p38 MAPK and Smad 2/3 pathways and EMT. Acta Pharmacol Sin, 42(8): 1280-7. [ DOI:10.1038/s41401-020-00596-y] 40. Zhao YY, Jia J, Zhang JJ, Xun YP, Xie SJ, Liang JF, et al. (2021) Inhibi tion of histamine receptor H3 suppresses the growth and metasta sis of human non-small cell lung cancer cells via inhibiting PI3K/Akt/mTOR and MEK/ERK signaling pathways and blocking EMT. Ac ta Pharmacol Sin, 42(8): 1288-97. [ DOI:10.1038/s41401-020-00548-6] 41. Zhang Y, Song D, Peng Z, Wang R, Li K, Ren H, et al. (2022) LINC00891 regulated by miR-128-3p/GATA2 axis impedes lung cancer cell proliferation, invasion and EMT by inhibiting RhoA pathway. Acta Biochim Biophys Sin (Shanghai), 54(3): 378-87. [ DOI:10.3724/abbs.2022005] 42. Chanvorachote P, Petsri K, Thongsom S (2022) Epithelial to Mesen chymal Transition in Lung Cancer: Potential EMT-targeting natural product-derived compounds. Anticancer Res, 42(9): 4237-46. [ DOI:10.21873/anticanres.15923] 43. Odero-Marah V, Hawsawi O, Henderson V, Sweeney J (2018) Epi thelial-mesenchymal transition (EMT) and prostate cancer. Adv Exp Med Biol, 1095: 101-10. [ DOI:10.1007/978-3-319-95693-0_6] 44. Li Q, Zhou ZW, Duan W, Qian CY, Wang SN, Deng MS, et al. (2021) Inhibiting the redox function of APE1 suppresses cervical cancer metastasis via disengagement of ZEB1 from E-cadherin in EMT. J Exp Clin Can Res, 40(1): 220. [ DOI:10.1186/s13046-021-02006-5] 45. Yang C, Xiao Y, Du Y, Xiong J, Deng L, Liang Q, et al. (2022) Iodine-125 seeds inhibit carcinogenesis of hepatocellular carcinoma cells by suppressing epithelial-mesenchymal transition via TGF-β1/Smad signaling. Disease Markers, 2022: 9230647. [ DOI:10.1155/2022/9230647] 46. Berr AL, Wiese K, Dos Santos G, Koch CM, Anekalla KR, Kidd M, et al. (2023) Vimentin is required for tumor progression and metasta sis in a mouse model of non-small cell lung cancer. Oncogene, 42(25): 2074-87. [ DOI:10.1038/s41388-023-02703-9] 47. Cao ZQ, Wang Z, Leng P (2019) Aberrant N-cadherin expression in cancer. Biomedicine & pharmacotherapy, 118: 109320. [ DOI:10.1016/j.biopha.2019.109320] 48. He Y, Li L, Liu J, Zhang X (2018) Iodine-125 seed brachytherapy in hibits non-small cell lung cancer by suppressing epithelial-mesenchymal transition. Brachytherapy, 17(4): 696-701. [ DOI:10.1016/j.brachy.2018.03.002] 49. Peng D, Fu M, Wang M, Wei Y, Wei X (2022) Targeting TGF-beta signal transduction for fibrosis and cancer therapy. Mol Cancer, 21(1): 104. [ DOI:10.1186/s12943-022-01569-x] 50. Hao Y, Baker D, Ten Dijke P (2019) TGF-beta-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis. Int J Mol Sci, 20(11): 2767. [ DOI:10.3390/ijms20112767] 51. Liu DK, Dong HF, Liu RF, Xiao XL (2020) Baicalin inhibits the TGF-beta1/p-Smad3 pathway to suppress epithelial-mesenchymal tran sition-induced metastasis in breast cancer. Oncotarget, 11(29): 2863-72. [ DOI:10.18632/oncotarget.27677] 52. Da C, Liu Y, Zhan Y, Liu K, Wang R (2016) Nobiletin inhibits epitheli al-mesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-beta1/Smad3 signaling pathway. On col Rep, 35(5): 2767-74. [ DOI:10.3892/or.2016.4661] 53. Liu X, Zhang Y, Zhou GJ, Hou Y, Kong Q, Lu JJ, et al. (2020) Natural alkaloid 8-oxo-epiberberine inhibited TGF-beta1-triggred epithelial-mesenchymal transition by interfering Smad3. Toxicol Appl Phar macol, 404: 115179. [ DOI:10.1016/j.taap.2020.115179] 54. Cho HJ, Baek KE, Saika S, Jeong MJ, Yoo J (2007) Snail is required for transforming growth factor-beta-induced epithelial-mesenchymal transition by activating PI3 kinase/Akt signal path way. Biochem Biophys Res Commun, 353(2): 337-43. [ DOI:10.1016/j.bbrc.2006.12.035] 55. Serrano-Gomez SJ, Maziveyi M, Alahari SK (2016) Regulation of ep ithelial-mesenchymal transition through epigenetic and post-translational modifications. Molecular Cancer, 15: 18. [ DOI:10.1186/s12943-016-0502-x]
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