放射线对人舌鳞癌细胞系Tca8113细胞生物学效应的影响
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摘要
目的探讨放射线治疗的分子机制,以更好地指导口腔鳞癌患者的临床放射治疗。方法以不同剂量(0、4、8、10 Gy)的放射线照射舌鳞癌Tca8113细胞,采用流式细胞仪检测细胞周期分布及凋亡,并在相差显微镜下观察细胞形态学变化。结果流式细胞仪分析结果显示,10 Gy放射线照射明显诱导了Tca8113细胞G2/M期阻滞和细胞凋亡,并且Tca8113细胞经10 Gy放射线照射后细胞形态发生了明显的变化。结论放射线照射可导致口腔癌细胞周期阻滞、凋亡和胀亡的形态学变化。
Objective To explore the molecular mechanism underlying the therapeutic effects of irradiation therapy in order to direct clinical radiation therapy of oral cancers. Methods After 0,4,8 and 10 Gy ionizing radiation( IR),the apoptosis and cell cycle of Tca8113 cells were detected with flow cytometry,and the morphological changes were observed with phase contract microscope. Results Flow cytometry analysis showed that 10 Gy irradiation significantly induced G2/M phase arrest and apoptosis,as well as morphologic changes of cells. Conclusion High-dose radiation exposure can cause cell cycle arrest and significant morphologic changes of apoptosis and oncosis in oral cancer cells.
Objective To explore the molecular mechanism underlying the therapeutic effects of irradiation therapy in order to direct clinical radiation therapy of oral cancers. Methods After 0,4,8 and 10 Gy ionizing radiation( IR),the apoptosis and cell cycle of Tca8113 cells were detected with flow cytometry,and the morphological changes were observed with phase contract microscope. Results Flow cytometry analysis showed that 10 Gy irradiation significantly induced G2/M phase arrest and apoptosis,as well as morphologic changes of cells. Conclusion High-dose radiation exposure can cause cell cycle arrest and significant morphologic changes of apoptosis and oncosis in oral cancer cells.
引文
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[3]Greenlee RT,Hill-harmon MB,Murray T,et al. Cancerstatistics,2001[J]. CA Cancer J Clin,2010,51(1):15-36.
[4] Jemal A,Siegel R,Ward E,et al. Cancer statistics,2007[J]. CA Cancer J Clin,2007,57(1):43-66.
[5] Peters LJ,Rodney Withers H,Thames HD Jr,et al.Keynote address:the problem:Tumor radioresistance inclinical radiotherapy[J]. Int J Radiat Oncol Biol Phys,1982,8(1):101-108.
[6]Deacon J,Peckham MJ,Steel GG. The radioresponsive-ness of human tumours and the initial slope of the cell sur-vival curve[J]. Radiother Oncol,1984,2(4):317-323.
[7]Desai AA,Latta ET,Spaulding A,et al. The impor-tance of routine HIV testing in the incarcerated popula-tion:the Rhode Island experience[J]. AIDS Educ Prev,2002,14(5 Suppl B):45-52.
[8]Reis T,Edgar BA. Negative Regulation of d E2F1 by cy-clin-dependent kinases controls cell cycle timing[J].Cell,2004,117(2):253-264.
[9]Sinclair WK,Morton RA. Variations in X-Ray responseduring the division cycle of partially synchronized Chinesehamster cells in culture[J]. Nature,1963,199:1158-1160.
[10]Sinclair WK,Morton RA. X-Ray and ultraviolet sensi-tivity of synchronized chinese hamster cells at variousstages of the cell cycle[J]. Biophys J,1965,5(1):1-25.
[11]Terasima T,Tolmach LJ. Variations in several responsesof He La cells to X-irradiation during the division cycle[J]. Biophysical Journal,1963,3(1):11-33.
[12]Shinomiya N. New concepts in radiation-induced apopto-sis:‘premitotic apoptosis’and‘postmitotic apoptosis’?[J]. J Cell Mol Med,2001,5(3):14.
[13]Mcilwrath AJ,Vasey PA,Ross GM,et al. Cell cyclearrests and radiosensitivity of human tumor cell lines:dependence on w ild-type p53 for radiosensitivity[J].Cancer Res,1994,54(14):3718-3722.
[14]Yount GL,Haas-Kogan DA,Vidair CA,et al. Cell cy-cle synchrony unmasks the influence of p53 function onradiosensitivity of human glioblastoma cells[J]. CancerRes,1996,56(3):500-506.
[15]Bristow RG,Jang A,Peacock J,et al. Mutant p53 in-creases radioresistance in rat embryo fibroblasts simulta-neously transfected w ith HPV16-E7 and/or activated H-ras[J]. Oncogene,1994,9(6):1527-1536.
[16] Komarova EA. Transgenic mice with p53-responsivelac Z:p53activity varies dramatically during normal de-velopment and determines radiation and drug sensitivityin vivo[J]. The EM BO Journal,1997,16(6):1391-1400.
[17]Merritt AJ,Potten CS,Kemp CJ,et al. The role of p53in spontaneous and radiation-induced apoptosis in thegastrointestinal tract of normal and p53-deficient mice[J]. Cancer Res,1994,54(3):614-617.
[18] Lowe SW,Schmitt EM,Smith SW,et al. p53 is re-quired for radiation-induced apoptosis in mouse thymo-cytes[J]. Nature,1993,362(6423):847-849.
[19]Brown KD,Lataxes TA,Shangary S,et al. Ionizing ra-diation exposure results in up-regulation of Ku70 via ap53/ataxia-telangiectasia-mutatedprotein-dependentmechanism[J]. J Biol Chem,2000,275(9):6651-6656.
[20] Herzog KH,Chong MJ,Kapsetaki M,et al. Require-ment for atm in ionizing radiation-induced cell death inthe developing central nervous system[J]. Science,1998,280(5366):1089-1091.
[21]Fei PW,Bernhard EJ,Eldeiry WS. Tissue-specific in-duction of p53 targets in vivo[J]. Cancer Res,2002,62(24):7316-7327.
[22]Lakhani SA,Masud A,Kuida K,et al. Caspases 3 and7:key mediators of mitochondrial events of apoptosis[J]. Science,2006,311(5762):847-851.
[23]Majno G,Joris I. Apoptosis,oncosis,and necrosis. Anoverview of cell death[J]. Am J Pathol,1995,146(1):3-15.
[24]Orlov SN,Hamet P. Apoptosis vs. oncosis:role of cellvolume and intracellular monovalent cations[J]. AdvExp M ed Biol,2004,559:219-233.
[25]高荣莲.大剂量γ射线照射后PC12细胞死亡方式的研究[J].中华放射医学与防护杂志,2006,26(5):449-452.
[26]Weerasinghe P,Buja LM. Oncosis:an important non-apoptotic mode of cell death[J]. Exp M ol Pathol,2012,93(3):302-308.
[27]Uversky VN,Cooper EM,Bower KS,et al. Acceler-atedα-synuclein fibrillation in crow ded milieu[J]. FebsLetters,2002,515(1-3):99-103.