Abstract：Autophagy extensively exists in eukaryotes,which utilizes lysosomes to degrade the damaged organelles or proteins,maintain the stability of the intracellular environment and provide energy. It can also participate in the growth,proliferation and apoptosis of tumor cells through autophagy-related genes and signaling pathways. Radiotherapy is one of the main treatments for cancer,whereas tumor cells often have radiation resistance, which reduces the clinical efficacy. Previous studies have demonstrated that autophagy is associated with the radiosensitivity of tumor cells, but the conclusions are different. In this article, different effects of autophagy upon the radiosensitity of tumor cells were reviewed.
[1]Yang Z,Klionsky DJ. An overview of the molecular mechanism of autophagy[J]. Curr Top Microbiol Immunol,2009,335(1):1-32. DOI:10.1007/978-3-642-00302-8_1. [2]毛建国,马瑞,赵丽娜,等. X线照射后鼻咽癌细胞自噬与转移关系及机制初探[J]. 中华放射肿瘤学杂志,2017,26(3):324-328. DOI:10.3760/cma.j.issn.1004-4221.2017.03.016. Mao JG,Ma R,Zhao LN,et al. X-ray setelah kanker nasofaring sel hubungan autophagy dan metastasis dan mekanisme eksplorasi awal dari jurnal Cina Radiasi Onkologi, 2017,26(3):324-328. DOI:10.3760/cma.j.issn.1004-4221.2017.03.016. [3]杨熙宇,赵国旗. 自噬与鼻咽癌放疗研究进展[J]. 辐射研究与辐射工艺学报,2017,35(8):050101. DOI:10.11889/j.1000-3436.2017.rrj.35.050101. Yang XY,Zhao GQ. Advances in autophagy and radiotherapy for nasopharyngeal carcinoma[J]. J Radiat Res Radiat Technol,2017,35(8):050101. DOI:10.11889/j.1000-3436.2017.rrj.35.050101. [4]Klionsky DJ. The molecular machinery of autophagy:unanswered questions[J]. J Cell Sci,2005,118(Pt 1):7-18. DOI:10.1242/jcs.01620. [5]Rubinsztein DC,Shpilka T,Elazar Z. Mechanisms of autophagosome biogenesis[J]. Curr Biol,2012,22(1):R29-34. DOI:10.1016/j.cub.2011.11.034. [6]Lorin S,HamaïA,Mehrpour M,et al. Autophagy regulation and its role in cancer[J]. Semin Cancer Biol.2013,23(5):361-379. DOI:10.1016/j.semcancer.2013.06.007. [7]曹建平,夏大静. 自噬与肿瘤关系研究新进展[J]. 浙江大学学报,2015,44(2):204-210. DOI:10.3785/j.issn.1008-9292.2015.03.014. Cao JP,Xia DJ. Recent advances in the relationship between autophagy and cancer[J]. J Zhejiang Univ,2015,44(2:2:204-210. DOI:10.3785/j.issn.1008-9292.2015.03.014. [8]Yang Z,Klionsky DJ. An overview of the molecular mechanism of autophagy[J]. Curr Top Microbiol Immunol,2009,335(1):1-32. DOI:10.1007/978-3-642-00302-8_1. [9]Sun A,Li C,Chen R,et al. GSK-3β controls autophagy by modulating LKB1-AMPK pathway in prostate cancer cells[J]. Prostate,2016,76(2):172-183. DOI:10.1002/pros.23106. [10]Chang L,Graham PH,Hao J,et al. PI3K/Akt/mTOR pathway inhibitors enhance radiosensitivity in radioresistant prostate cancer cells through inducing apoptosis,reducing autophagy,suppressing NHEJ and HR repair pathways[J]. Cell Death Dis,2014,5:e1437. DOI:10.1038/cddis.2014.415. [11]Takeuchi H,Kondo Y,Fujiwara K,et al. Synergistic augmentation of rapamycin-induced autophagy in malignant glioma cells by phosphatidylinositol 3-kinase/protein kinase B inhibitors[J]. Cancer Res,2005,65(8):3336-3346. DOI:10.1158/0008-5472. CAN-04-3640. [12]Mrakovcic M,Fröhlich LF.p53-Mediated Molecular Control of Autophagy in Tumor Cells[J]. Biomolecules,2018,8(2):14. DOI:10.3390/biom8020014. [13]Hosokawa N,Hara T,Kaizuka T,et al. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy[J]. Mol Biol Cell,2009,20(7):1981-1991. DOI:10.1091/mbc.e08-12-1248. [14]Kim J,Kundu M,Viollet B,et al. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1[J]. Nat Cell Biol,2011,13(2):132-141. DOI:10.1038/ncb2152. [15]Yang Z,Klionsky DJ. Mammalian autophagy:core molecular machinery and signaling regulation[J]. Curr Opin Cell Biol,2010,22(2):124-131. DOI:10.1016/j.ceb.2009.11.014. [16]Tanida I,Ueno T,Kominami E. LC3 and autophagy[J]. Meth Mol Biol,2008,445(1):77-88. DOI:10.1007/978-1-59745-157-4_4. [17]Shimizu S,Yoshida T,Tsujioka M,et al. Autophagic cell death and cancer[J]. Int J Mol Sci,2014,15(2):3145-3153. DOI:10.3390/ijms15023145. [18]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. DOI:10.1016/j.radonc.2011.06.002. [19]Chen Y,Li X,Guo L,et al. Combining radiation with autophagy inhibition enhances suppression of tumor growth and angiogenesis in esophageal cancer[J]. Mol Med Rep,2015,12(2):1645-1652. DOI:10.3892/mmr.2015.3623. [20]Wang F,Tang J,Li P,et al. Chloroquine enhances the radiosensitivity of bladder cancer cells by inhibiting autophagy and activating apoptosis[J]. Cell Physiol Biochem,2018,45(1):54-66. DOI:10.1159/000486222. [21]Ye H,Chen M,Cao F,et al. Chloroquine,an autophagy inhibitor,potentiates the radiosensitivity of glioma initiating cells by inhibiting autophagy and activating apoptosis[J]. BMC Neurol,2016,16(1):178. DOI:10.1186/s12883-016-0700-6. [22]Kimura T,Takabatake Y,Takahashi A,et al. Chloroquine in cancer therapy:a double-edged sword of autophagy[J]. Cancer Res,2013,73(1):3-7. DOI:10.1158/0008-5472. CAN-12-2464. [23]Wu YT,Tan HL,Shui G,et al. Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class Ⅰ and Ⅲ phosphoinositide 3-kinase[J]. J Biol Chem,2010,285(14):10850-10861. DOI:10.1074/jbc. M109.080796. [24]Feng H,Wang J,Chen W,et al. Hypoxia-induced autophagy as an additional mechanism in human osteosarcoma radioresistance[J]. J Bone Oncol,2016,5(2):67-73. DOI:10.1016/j.jbo.2016.03.001. [25]Koukourakis MI,Giatromanolaki A,Fylaktakidou K,et al. SMER28 is a mTOR-independent small molecule enhancer of autophagy that protects mouse bone marrow and liver against radiotherapy[J]. Invest New Drugs,2018,36(5):773-781. DOI:10.1007/s10637-018-0566-0. [26]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):2720-31. DOI:10.1002/ijc.25975. [27]Li Y,Liu F,Wang Y,et al. Rapamycin-induced autophagy sensitizes A549 cells to radiation associated with DNA damage repair inhibition[J]. Thorac Cancer,2016,7(4):379-386. DOI:10.1111/1759-7714.12332. [28]Lin CI,Whang EE,Donner DB,et al. Autophagy induction with RAD001 enhances chemosensitivity and radiosensitivity through Met inhibition in papillary thyroid cancer[J]. Mol Cancer Res,2010,8(9):1217-1226. DOI:10.1158/1541-7786. MCR-10-0162. [29]He JH,Liao XL,Wang W,et al. Apogossypolone,a small-molecule inhibitor of Bcl-2,induces radiosensitization of nasopharyngeal carcinoma cells by stimulating autophagy[J]. Int J Oncol,2014,45(3):1099-1108. DOI:10.3892/ijo.2014.2497. [30]Zhuang W,Li B,Long L,et al. Knockdown of the DNA-dependent protein kinase catalytic subunit radiosensitizes glioma-initiating cells by inducing autophagy[J]. Brain Res,2011,1371(1):7-15. DOI:10.1016/j.brainres.2010.11.044. [31]Bristol ML,Emery SM,Maycotte P,et al. Autophagy inhibition for chemosensitization and radiosensitization in cancer:do the preclinical data support this therapeutic strategy?[J]. J Pharmacol Exp Ther,2013,344(3):544-552. DOI:10.1124/jpet.112.199802. [32]Wilson EN,Bristol ML,Di X,et al. A switch between cytoprotective and cytotoxic autophagy in the radiosensitization of breast tumor cells by chloroquine and vitamin D[J]. Horm Cancer,2011,2(5):272-285. DOI:10.1007/s12672-011-0081-7. [33]Sharma K,Goehe RW,Di X,et al. A novel cytostatic form of autophagy in sensitization of non-small cell lung cancer cells to radiation by vitamin D and the vitamin D analog,EB 1089[J]. Autophagy,2014,10(12):2346-2361. DOI:10.4161/15548627.2014.993283.
2019, Vol. 28 
