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| 1 | Autophagy inhibition by chloroquine sensitizes HT-29 colorectal cancer cells to concurrent chemoradiation显示文摘AIM:To investigate whether the inhibition of autophagy by chloroquine(CQ)sensitizes rectal tumors to radiation therapy(RT)or concurrent chemoradiation(chemoRT).METHODS:In vitro,HCT-116 and HT-29 colorectal cancer(CRC)cell lines were treated as following:(1)PBS;(2)CQ;(3)5-fluorouracil(5-FU);(4)RT;(5)CQ and RT;(6)5-FU and RT;(7)CQ and 5-FU;and(8)5-FU and CQ and RT.Each group was then exposed to various doses of radiation(0-8 Gy)depending on the experiment.Cell viability and proliferative capacity were measured by3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and clonogenic assays.Clonogenic survivalcurves were constructed and compared across treatment groups.Autophagy status was determined by assessing the LC3-Ⅱto LC3-Ⅰratio on western blot analysis,autophagosome formation on electron microscopy and identification of a perinuclear punctate pattern with GFPlabeled LC3 on fluorescence microscopy.Cell cycle arrest and cell death were evaluated by FACS and AnnexinⅤanalysis.All experiments were performed in triplicate and statistical analysis was performed by the student’s t test to compare means between treatment groups.RESULTS:RT(2-8 Gy)induced autophagy in HCT-116and HT-29 CRC cell lines at 4 and 6 h post-radiation,respectively,as measured by increasing LC3-Ⅱto LC3-Ⅰratio on western blot.Additionally,electron microscopy demonstrated autophagy induction in HT-29 cells24 h following irradiation at a dose of 8 Gy.Drug treatment with 5-FU(25μmol/L)induced autophagy and the combination of 5-FU and RT demonstrated synergism in autophagy induction.CQ(10μmol/L)alone and in combination with RT effectively inhibited autophagy and sensitized both HCT-116 and HT-29 cells to treatment with radiation(8 Gy;P<0.001 and 0.00001,respectively).Significant decrease in clonogenic survival was seen only in the HT-29 cell line,when CQ was combined with RT at doses of 2 and 8 Gy(P<0.5 and P=0.05,respectively).There were no differences in cell cycle progression or Annexin V staining upon CQ addition to RT.CONCLUSION:Autophagy inhibition by CQ increases CRC cell sensitivity to concurrent treatment with 5-FU and RT in vitro,suggesting that addition of CQ to chemoRT improves CRC treatment response. | Caitlin A Schonewolf Monal Mehta Devora Schiff Hao Wu Bruce G Haffty Vassiliki Karantza Salma K Jabbour | 2014 | World Journal of Gastrointestinal Oncology2014，6，3： | 12 |
| 2 | Autophagy Opposes p53-Mediated Tumor Barrier to Facilitate Tumorigenesis in a Model of PALB2-Associated Hereditary Breast Cancer显示文摘 | Yanying Huo Hong Cai Irina Teplova Christian Bowman-Colin Guanghua Chen Sandy Price Nicola Barnard Shridar Ganesan Vassiliki Karantza Eileen White Bing Xia | 2013 | Cancer Discovery2013，，8： | 2 |
| 3 | Autophagy as a thempeutic target in cancer 显示文摘 | Chen N Karantza V | 2011 | Cancer Biol Ther2011，11，2： | 1 |
| 4 | Role of autophagy in cancer显示文摘 | Mathew R Karantza Wadsworth V White E | 2007 | Nat Rev Cancer2007，7，12： | 1 |
| 5 | Intentions to quit work among care staff working in the aged care sector 显示文摘 | Karantzas Gery C Mellor David McCabe Marita P | 2012 | The Gerontologist2012，52，4： | 1 |
| 6 | The interplay between autophagy and ros in tumorigenesis显示文摘 | Kongara S Karantza V | 2012 | Front Oncol2012，2，1： | 1 |
| 7 | Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis显示文摘 | Karantza Wadsworth V Pate1 S Kravchuk O | 2007 | Genes Dev2007，21，13： | 1 |
| 8 | Knowledge of late-life depression: An empirical investigation of aged care staff显示文摘 | Tanya E. Davison Marita P. McCabe David Mellor Gery Karantzas Kuruvilla George | 2009 | Aging & Mental Health2009，，4： | 1 |
| 9 | Autophagy and cancer cell metabolism 显示文摘 | Lozy F Karantza V | 2012 | Seminars in Cell & Developmenta| Biology2012，93，4： | 1 |
| 10 | Keratins in health and cancer:more than mere epithelial cell markers 显示文摘 | Karantza V | 2011 | Oncogene2011，30，2： | 1 |
| 11 | Thought processes associated withreluctance in gay men to be tested for HIY显示文摘 | Gold RS Karantzas G | 2008 | Int J STD AIDS2008，19，： | 1 |
| 12 | Thought processes associated with reluc- tance in gay men to be tested for HIV 显示文摘 | Gold RS Karantzas G | 2008 | Int J STD AIDS2008，19，11： | 1 |
| 13 | Autophagy and cancer cell metabolism显示文摘 | Lozy F Karantza V | 2012 | SeminCell Dev Biol2012，23，4： | 1 |
| 14 | Autophagy as a therapeutic target in cancer显示文摘 | Chen N Karantza V | 2011 | Cancer Biol Ther2011，1，2： | 1 |
| 15 | Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis显示文摘 | Karantza Wadsworth V Patel S Kravchuk O | 2007 | Genes Dev2007，21，13： | 1 |
| 16 | The interplay between autophagy and ROS in tumorigenesis显示文摘 | Kongara S Karantza V | 2012 | Front Oncol2012，2，： | 1 |
| 17 | Keratins in health and cancer: more than mere epithelial cell markers显示文摘 | Karantza V | 2011 | Oncogene2011，30，2： | 1 |
| 18 | On the Effect of Temper- ature on the Creep Behavior of Neat and Carbon Fiber Reinforced PEEK and Epoxy Resin 显示文摘 | Maulik D Karantza M Spandou E | 1995 | Journal of Composite Materials1995，29，3： | 1 |
| 19 | Autophagy as a therapeutic target in can(er 显示文摘 | Chen N Karantza V | 2011 | Cancer Biol Ther2011，11，2： | 1 |
| 20 | Role of au- tophagy in cancer显示文摘 | Mathew R Karantza - Wadsworth V White E | 2007 | Nat Rev Cancer2007，7，12： | 1 |
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