-
1946年,Robert Wilso首先提出了粒子治疗的设想[1],1954年在美国Lawrence Berkeley实验室进行了第一例肿瘤患者的粒子治疗[2]。质子和重离子射线治疗是近5年临床应用增加较快的粒子放疗技术。质子是指氢原子剥去电子后带有正电荷的粒子;重离子是指原子序数≥2的剥离或者部分剥离外围电子后的带正电荷的原子核,即比粒子4He重的离子,如12C、22Ne、45Ca等。质子重离子射线与常规光子射线相比具有更好的放射物理学和生物学特性,是目前最先进的放疗技术[3]。本文以碳离子为例,概述碳离子射线的物理和生物学特性,并着重综述其在诱导细胞凋亡方面的进展。
碳离子射线诱导细胞凋亡的研究进展
Progress in cell apoptosis induced by carbon ion beam
-
摘要: 碳离子射线治疗肿瘤是利用其剂量分布优势,将能量集中于肿瘤组织释放,同时尽量避免损伤周围正常组织。相较于常规光子射线,碳离子不仅表现出上述物理学优势,还具有优越的生物学特性。笔者概述了碳离子射线在物理、生物学方面的特点,并着重综述了其在诱导细胞凋亡方面的进展。Abstract: Compared with conventional radiation beams, heavy ion beam excels in its physical properties and biological characteristics. Limited energy release is absorbed by normal tissue before reaching the tumor while the energy bursts at the target region. This review presents the physical properties and biological characteristics of carbon ion beam and emphasizes recent progresses on apoptosis.
-
Key words:
- Carbon ion /
- Cell apoptosis /
- Neoplasms
-
[1] Hall E. Protons for radiotherapy:a 1946 proposal[J]. Lancet Oncol, 2009, 10(2):196. DOI:10.1016/s1470-2045(09)70022-1. [2] Tobias CA, Lyman JT, Chatterjee A, et al. Radiological physics characteristics of the extracted heavy ion beams of the bevatron[J].Science, 1971, 174(4014):1131-1134. DOI:10.1126/science.174.4014.1131. [3] Okayasu R. Repair of DNA damage induced by accelerated heavy ions-a mini review[J]. Inter J Cancer, 2012, 130(5):991-1000. DOI:10.1002/ijc.26445. [4] Matsumoto Y, Matsuura T, Wada M, et al. Enhanced radiobiological effects at the distal end of a clinical proton beam:in vitro study[J]. J Radiat Res, 2014, 55(4):816-822.DOI:10.1093/jrr/rrt230. [5] Loeffler JS, D urante M. Charged particle therapy-optimization, challenges and future directions[J]. Nat Rev Clin Oncol, 2013, 10(7):411-424. DOI:10.1038/nrclinonc.2013.79. [6] Yoo SH, Cho I, Cho S, et al. Effective Generation of the spread-out-Bragg peak from the laser accelerated proton beams using a carbon-proton mixed target[J]. Australas Phys Eng Sci Med, 2014, 37(4):635-644. DOI:10.1007/s13246-014-0292-7. [7] Paganetti H.Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and linear energy transfer[J]. Phys Med Biol, 2014, 59(22):R419-R472. DOI:10.1088/0031-9155/59/22/R419. [8] Held KD, Kawamura H, Kaminuma T, et al. Effects of charged particles on human tumor cells[J/OL]. Front Oncol, 2016, 6: 23[2017-11-10]. https://www.frontiersin.org/articles/10.3389/fonc.2016.00023/full. DOI: 10.3389/fonc.2016.00023. [9] Tsujii H, Kamada T. A review of update clinical results of Carbon ion radiotherapy[J]. Jpn J Clin Oncol, 2012, 42(8):670-685. DOI:10.1093/jjco/hys104. [10] Alexander BM, Pinnell N, Wen PY, et al.Targeting DNA repair and the cell cycle in glioblastoma[J]. J Neurooncol, 2012, 107(3):463-477.DOI:10.1007/s11060-011-0765-4. [11] Suetens A, Konings K, Moreels M, et al. Higher initial DNA damage and persistent cell cycle arrest after Carbon ion irradiation compared to X-irradiation in prostate and colon cancer cells[J/OL]. Front Oncol, 2016, 6: 87[2017-11-10]. https://www.frontiersin.org/articles/10.3389/fonc.2016.00087/full. DOI: 10.3389/fonc.2016.00087. [12] Wang H, Liu S, Zhang P, et al. S-phase cells are more sensitive to high-linear energy transfer radiation[J]. Int J Radiat Oncol Biol Phys, 2009, 74(4):1236-1241. DOI:10.1016/j.ijrobp.2008.12.089. [13] Hirayama R, Uzawa A, Obara M, et al. Determination of the relative biological effectiveness and Oxygen enhancement ratio for micronuclei formation using high-LET radiation in solid tumor cells:An in vitro and in vivo study[J]. Mut Res Genet Toxicol Environ Mutagen, 2015, 793:41-47. DOI:10.1016/j.mrgentox.2015.08.003. [14] Lin BR, Li D, Zhang L. Oxymatrine mediates Bax and Bcl-2 expression in human breast cancer MCF-7 cells[J]. Pharmazie, 2016, 71(3):154-157. DOI:10.1691/ph.2016.5765. [15] Li C, Wu X, Sun R, et al.Croton tiglium extract induces apoptosis via Bax/Bcl-2 pathways in human lung cancer a549 cells[J]. Asian Pac J Cancer Prev, 2016, 17(11):4893-4898. DOI:10.22034/APJCP.2016.17.11.4893. [16] Khodapasand E, Jafarzadeh N, Farrokhi F, et al. Is Bax/Bcl-2 ratio considered as a prognostic marker with age and tumor location in colorectal cancer?[J]. Iran Biomed J, 2015, 19(2):69-75. DOI:10. 6091/ibj.1366.2015. [17] Delbridge AR, Grabow S, Strasser A, et al.Thirty years of Bcl-2:translating cell death discoveries into novel cancer therapies[J]. Nat Rev Cancer, 2016, 16(2):99-109. DOI:10.1038/nrc.2015.17. [18] Hamada N, Hara T, Omura-Minamisawa MA, et al. Energetic heavy ions overcome tumor radioresistance caused by overexpression of Bcl-2[J]. Radiother Oncol, 2008, 89(2):231-236. DOI:10.1016/j.radonc.2008.02.013. [19] Sato T, Hamada N. Model assembly for estimating cell surviving fraction for both targeted and nontargeted effects based on microdosimetric probability densities[J/OL]. PLoS One, 2014, 9(11): 0114056[2017-11-10]. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0114056. DOI: 10.1371/journal.pone.0114056. [20] Xue L, Furusawa Y, Okayasu R, et al.The complexity of DNA double Strand break is a crucial factor for activating ATR signaling pathway for G2/M checkpoint regulation regardless of ATM function[J]. DNA repair, 2015, 25:72-83. DOI:10.1016/j.dnarep.2014.11.004. [21] Di CX, Yang LN, Zhang H, et al. Effects of carbon-ion beam or X-ray irradiation on anti-apoptosisΔNp73 expression in HeLa cells[J].Gene, 515(1):208-213. DOI:10.1016/j.gene.2012.11.040. [22] Abdelhaleem EF, Abdelhameid MK, Kassab AE, et al. Design and synthesis of thienopyrimidine urea derivatives with potential cytotoxic and pro-apoptotic activity against breast cancer cell line MCF-7[J]. Eur J Med Chem, 2018, 143:1807-1825. DOI:10.1016/j.ejmech, 2017.10.075. [23] Moshrefi M, Spotin A, Kafil HS, et al. Tumor suppressor p53 induces apoptosis of host lymphocytes experimentally infected by Leishmania major, by activation of Bax and caspase-3:a possible survival mechanism for the parasite[J]. Parasitol Res, 2017, 116(8):2159-2166. DOI:10.1007/s00436-017-5517-8. [24] Song HY, Deng XH, Yuan GY, et al. Expression of bcl-2 and p53 in induction of esophageal cancer cell apoptosis by ECRG2 in combination with cisplatin[J]. Asian Pa J Cancer Prev, 2014, 15(3):1397-1401.DOI:10.7314/APJCP.2014.15.3.1397. [25] Zhao YF, Wang LX, Huang QY, et al.Radiosensitization of non-small cell lung cancer cells by inhibition of TGF-beta 1 signaling with SB431542 is dependent on p53 status[J]. Oncol Res, 2016, 24(1):1-7. DOI:10.3727/096504016X14570992647087. [26] Mirzayans R, Andrais B, Scott A, et al. New insights into p53 signaling and cancer cell response to DNA damage: implications for cancer therapy[J/OL]. J Biomed Biotechnol, 2012: 170325[2017-11-10]. https://www.hindawi.com/journals/bmri/2012/170325/. DOI: 10.1155/2012/170325. [27] Amornwichet N, Oike T, Shibata AA, et al. Carbon-Ion beam irradiation kills X-ray-resistant p53-Null cancer cells by inducing mitotic catastrophe[J/OL]. PLoS One, 2014, 9(12): 0115121[2017-11-10]. http://dx.org/10.1371/journal.pone.0115121. DOI: 10.1371/journal.pone.0115121. [28] He M, Dong C, Konishi T, et al. Differential effects of p53 on bystander phenotypes induced by gamma ray and high LET heavy ion radiation[J]. Life Sci Space Res(Amst), 2014, 1:53-59. DOI:10.1016/j.lssr.2014.02.003. [29] Nakagawa Y, Takahashi A, Kajihara AA, et al. Depression of p53-independent Akt survival signals in human oral cancer cells bearing mutated p53 gene after exposure to high-LET radiation[J].Biochem Biophys Res Commun, 2012, 423(4):654-660. DOI:10. 1016/j.bbrc.2012.06.004. [30] Liu K, Zhao XK, Gu J, et al.Effects of C-12(6+) heavy ion beam irradiation on the p53 signaling pathway in HepG2 liver cancer cells[J]. Acta Biochim Biophys Sin (Shanghai), 2017, 49(11):989-998. DOI:10.1093/abbs/gmx096. [31] Alphonse G, Maalouf M, Battiston MP, et al. p53-independent early and late apoptosis is mediated by ceramide after exposure of tumor cells to photon or Carbon ion irradiation[J]. BMC Cancer, 2013, 13:151. DOI:10.1186/1471-2407-13-151. [32] Yamakawa N, Takahashi A, Mori E, et al. High LET radiation enhances apoptosis in mutated p53 cancer cells through Caspase-9 activation[J]. Cancer Sci, 2008, 99(7):1455-1460. DOI:10.1111/j.1349-7006.2008.00818.x. [33] Tomiyama A, Tachibana K, Suzuki K, et al. MEK-ERK-dependent multiple caspase activation by mitochondrial proapoptotic Bcl-2 family proteins is essential for heavy ion irradiation-induced glioma cell death[J/OL]. Cell Death Disease, 2010, 1: e60[2017-11-10]. https://www.nature.com/articles/cddis201037. DOI: 10.1038/cddis,2010.37. [34] Xu H, Gao L, Che TJ, et al.The effects of C-12(6+) irradiation on cell cycle, apoptosis, and expression of caspase-3 in the human lung cancer cell line H1299[J]. Cancer Biotherapy Radiopharm, 2012, 27(2):113-118. DOI:10.1089/cbr.2011.1037. [35] Ghorai A, Bhattacharyya NP, Sarma A, et al. Radiosensitivity and induction of apoptosis by high LET Carbon ion beam and low LET gamma radiation: a comparative study[J/OL]. Scientifica (Cairo), 2014: 438030[2017-11-10]. https://www.hindawi.com/journals/scientifica/2014/438030/.DOI:10.1155/2014/438030" target="_blank">10.1155/2014/438030">https://www.hindawi.com/journals/scientifica/2014/438030/.DOI:10.1155/2014/438030. [36] Ghorai A, Sarma A, Bhattacharyya NP. Carbon ion beam triggers both caspase-dependent and caspase-independent pathway of apoptosis in HeLa and status of PARP-1 controls intensity of apoptosis[J]. Apoptosis, 2015, 20(4):562-580. DOI:10.1007/s10495-015-1107-3.