肿瘤微环境与肿瘤细胞放射敏感性关系的研究进展

doi:10.13481/j.1671-587x.20160540

摘要/Abstract

摘要：

肿瘤放射治疗（放疗）是肿瘤治疗的重要手段之一。然而，电离辐射等因素可改变肿瘤微环境，而其微环境对电离辐射产生抵抗性，降低肿瘤细胞的放射敏感性，这已成为肿瘤放疗的瓶颈、复发的根源。为此，本文主要综述肿瘤微环境中肿瘤细胞放射敏感性的差异、缺氧微环境诱导肿瘤细胞的辐射抗性、肿瘤细胞DNA损伤修复与放射敏感性、肿瘤基质和干细胞对放射敏感性的影响及肿瘤细胞凋亡和自噬与放射敏感性等方面内容，以加深对肿瘤微环境与肿瘤细胞放射敏感性之间关系的理解，并对辐射抗性的肿瘤细胞及其肿瘤干细胞采取可能的干预措施，达到有效治疗肿瘤的目的。

关键词: 肿瘤细胞, 肿瘤微环境, 电离辐射, 放射敏感性, 辐射抗性

中图分类号:

R730.55

张玉宇, 王利波, 赵钦, 李戈, 龚守良, 董丽华. 肿瘤微环境与肿瘤细胞放射敏感性关系的研究进展[J]. 吉林大学学报(医学版), 2016, 42(05): 1038-1044.

参考文献

[1] 朱广迎. 放射肿瘤学[M]. 2版. 北京:科学技术文献出版社, 2005.

[2] Steel GG, McMillan TJ, Peacock JH. The 5Rs of radiobiology[J]. Int J Radiat Biol, 1989, 56(6):1045-1048.

[3] Hall JS, Iype R, Senra J, et al. Investigation of radiosensitivity gene signatures in cancer cell lines[J]. PLoS One, 2014, 9(1):e86329.

[4] 龚守良. 辐射细胞生物学[M].北京:中国原子能出版社, 2014:55-57.

[5] 孙建湘, 孙伟建, 隋建丽, 等. DNA双链断裂残留损伤与癌细胞辐射敏感性研究[J]. 中华放射医学与防护杂志, 2008, 28(5):495-499.

[6] Gurská S, Farkasová T, Gábelová A. Radiosensitivity of cervical cancer cell lines:the impact of polymorphisms in DNA repair genes[J]. Neoplasma, 2007, 54(3):195-201.

[7] Clarke RH, Moosa S, Anzivino M, et al. Sustained radiosensitization of hypoxic glioma cells after oxygen pretreatment inan animal model of glioblastoma and in vitro models of tumor hypoxia[J]. PLoS One, 2014, 9(10):e111199.

[8] Zhang YC, Jiang G, Gao H, et al. Influence of ionizing radiation on ovarian carcinoma SKOV-3 xenografts in nude mice under hypoxic conditions[J]. Asian Pac J Cancer Prev, 2014, 15(5):2353-2358.

[9] He WS, Dai XF, Jin M, et al. Hypoxia-induced autophagy confers resistance of breast cancer cells to ionizing radiation[J]. Oncol Res, 2012, 20(5/6):251-258.

[10] Liu C, Lin Q, Yun Z. Cellular and molecular mechanisms underlyingoxygen-dependent radiosensitivity[J]. Radiat Res, 2015, 183(5):487-496.

[11] Li ZZ, Bao SD, Wu QL, et al. Hypoxia-Inducible factors Regulate tumorigenic capacity of glioma stem cells[J]. Cancer Cell, 2009, 15(6):501-513.

[12] Heddleston JM, Li Z, Lathia JD, et al. Hypoxia inducible factors in cancer stem cells[J]. Br J Cancer, 2010, 102(5):789-795.

[13] Li L, Neaves WB. Normal stem cells and cancer stem cells:the niche matters[J]. Cancer Res, 2006, 66(9):4553-4557.

[14] Bao S, Wu Q, McLendon RE, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response[J]. Nature, 2006, 444(7120):756-760.

[15] Marie-Egyptienne DT, Lohse I, Hill RP. Cancer stem cells, the epithelial to mesenchymal transition (EMT) and radioresistance:potential role of hypoxia[J]. Cancer Lett, 2013, 341(1):63-72.

[16] Hennequin C, Quero L, Favaudon V. DNA repair and tumour radiosensitivity:focus on ATM gene[J]. Bull Cancer, 2011, 98(3):239-246.

[17] Kumar A, Rai PS, Upadhya R, et al. γ-radiation induces cellular sensitivity and aberrant methylation in human tumor cell lines[J]. Int J Radiat Biol, 2011, 87(11):1086-1096.

[18] Eyler CE, Rich JN. Survival of the fittest:cancer stem cells in therapeutic resistance and angiogenesis[J]. Clin Oncol, 2008, 26(17):2893-2845.

[19] Wang X, Ma Z, Xiao Z, et al. Chk1 knockdown confers radiosensitization in prostate cancer stem cells[J]. Oncol Rep, 2012, 28(6):2247-2254.

[20] Phillips TM, McBride WH, Pajonk F. The response of CD24^-/low/CD44⁺ breast cancer-initiating cells to radiation[J]. J Natl Cancer Inst, 2006, 98(24):1777-1785.

[21] Croker AK, Allan AL. Inhibition of aldehyde dehydrogenase (ALDH) activity reduces chemotherapy and radiation resistance of stem-like ALDHhi CD44⁺ human breast cancer cells[J]. Breast Cancer Res Treat, 2012, 133(1):75-87.

[22] Sun T, Zhang Z, Li B, et al. Boron neutron capture therapy induces cell cycle arrest and cell apoptosis of glioma stem/progenitor cells in vitro[J]. Radiat Oncol, 2013, 8(1):195.

[23] 田允鸿, 谢国柱, 任陈, 等. 悬浮培养乳腺癌干细胞放疗抵抗与G2期阻滞相关[J]. 南方医科大学学报, 2011, 31(1):53-56.

[24] Ropolo M, Daga A, Griffero F, et al. Comparative analysis of DNA repair in stem and nonstem glioma cell culture[J]. Mol Cancer Res, 2009, 7(3):383-392.

[25] Yin H, Glass J. The phenotypic radiation resistance of CD44+/CD24(-or low) breast cancer cells is mediated through the enhanced activation of ATM signaling[J]. PLoS One, 2011, 6(9):e24080.

[26] Kim SY, Rhee JG, Song XX, et al. Breast cancer stem cell-like cells are more sensitive to ionizing radiation than non-stem cells:Role of ATM[J]. PLoS One, 2012, 7(11):e50423.

[27] Sun Y, Nelson PS. Molecular pathways:Involving microenvironment damage responses in cancer therapy resistance[J]. Clin Cancer Res, 2012, 18(15):4019-4025.

[28] John-Aryankalayil M, Palayoor ST, Cerna D, et al. Fractionated radiation therapy can induce a molecular profile for therapeutic targeting[J]. Radiat Res, 2010, 174:446-458.

[29] Chargari C, Clemenson C, Martins I, et al. Understanding the functions of tumor stroma in resistance to ionizing radiation:emerging targets for pharmacological modulation[J]. Drug Resist Updat, 2013, 16(1/2):10-21.

[30] Atkinson MJ. Radiation treatment effects on the proteome of the tumour microenvironment[J]. Adv Exp Med Biol, 2013, 990:49-60.

[31] D'Andrea FP. Intrinsic radiation resistance of mesenchymal cancer stem cells and implications for treatment response in a murine sarcoma model[J]. Dan Med J, 2012, 59(2):B4388.

[32] H ckel M, Vaupel P. Tumor hypoxia:definitions and current clinical, biologic, and molecular aspects[J]. J Natl Cancer Inst, 2001, 93(4):266-276.

[33] Phillips TM, McBride WH, Pajonk F. The response of CD24-/low/CD44+ breast cancer-initiating cells to radiation[J]. J Natl Cancer Inst, 2006, 98(24):1777-1785.

[34] Hardee ME, Marciscano AE, Medina-Ramirez CM, et al. Resistance of glioblatoma initiating cells to radiation mediated by the tumor microenvironment can be abolished by inhibiting transforming growth faxtor-β (TGFβ)[J]. Cancer Res, 2012, 72(16):4119-4129.

[35] Ahmed SU, Carruthers R, Gilmour L, et al. Selective inhibition of parallel DNA damage response pathways optimizes radiosensitization of glioblastoma stem-like cells[J]. Cancer Res, 2015, 75(20):4416-4428.

[36] Teng BT, Pei XM, Tam EW, et al. Opposing responses of apoptosis and autophagy to moderate compression in skeletal muscle[J]. Acta Physiol (Oxf), 2011, 201(2):239-254.

[37] Di CX, Yang LN, Zhang H, et al. Effects of carbon-ion beam or X-ray irradiation on anti-apoptosis ΔNp73 expression in HeLa cells[J]. Gene, 2013, 515(1):208-213.

[38] Wang WJ, Long LM, Yang N, et al. NVP-BEZ235, a novel dual PI3K/mTOR inhibitor, enhances the radiosensitivity of human glioma stem cells in vitro[J]. Acta Pharmacol Sin, 2013, 34(5):681-690.

[39] Zeng XH, Kinsella TJ. Impact of autophagy on chemotherapy and radiotherapy mediated tumor cytotoxicity: "to live or not to live"[J]. Front Oncol, 2011, 1:30.

[40] 齐亚莉, 王俊, 李岩, 等. 电离辐射联合自噬和凋亡抑制剂或诱导剂对MCF7细胞的影响[J]. 中华放射医学与防护杂志, 2010, 30(3):263-266.

[41] 陈清凤, 朱永坚, 曾群力. 射线诱发的细胞自噬效应的研究进展[J]. 中国劳动卫生职业病杂志, 2011, 29(6):473-475.

[42] Chaachouay H, Ohneseit P, Toulany M, et al. Autophagy contributes to resistance of tumor cells to ionizing radiation[J]. Radiother Oncol, 2011, 99(3):287-292.

[43] Yu L, Alva A, Su H, et al. Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8[J]. Science, 2004, 304(5676):1500-1502.

[44] Zhong R, Xu H, Chen G, et al. The role of hypoxia-inducible factor-1α in radiation-induced autophagic cell death in breast cancer cells[J]. Tumour Biol, 2015, 36(9):7077-7083.

[45] Sun Y, Xing X, Liu Q, et al. Hypoxia-induced autophagy reduces radiosensitivity by the HIF-1α/miR-210/Bcl-2 pathway in colon cancer cells[J]. Int J Oncol, 2015, 46(2):750-756.

[46] Vessoni AT, Muotri AR, Okamoto OK. Autophagy in stem cell maintenance and differentiation[J]. Stem Cells Dev, 2012, 21(4):513-520.

[47] Zhuang W, Li B, Long L, et al. Induction of autophagy promotes differentiation of glioma-initiating cells and their radiosensitivity[J]. Int J Cancer, 2011, 129(11):2720-2731.