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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 | Feeding-deterreney of oleanolic acid isolated from Panax quinquefolium against lepidopterans显示文摘 | Shukla Y N Tripathi A K Mehta V K | 1997 | Phytotherapy Research1997，11，8： | 1 |
| 3 | Effects of aspirin dose when used alone or in combination with clopidogrel inpatients with acute coronary syndromes:observations from the Clopidogrel in Unstable angina to prevent Recurrent Events(CURE)study显示文摘 | Peters R J Mehta S R Fox K A | 2003 | Circulation2003，108，14： | 1 |
| 4 | 查看详情显示文摘 | Haynam C A Wegner P J Auerbach J M Bowers M W Dixit S N Erbert G V Heestand G M Henesian M A Hermann M R Jancaitis K S Manes K R Marshall C D Mehta N C Menapace J Moses E Murray J R Nostrand M C Orth C D Patterson R SacksR A Shaw M J Spaeth M Sutton S B W | | 0，，： | 1 |
| 5 | Anomalous acid reaction rates in carbonate reservoir rock显示文摘 | TAYLOR K C NASR-EL-DINH A MEHTA S | 2006 | SPE Journal2006，11，4： | 1 |
| 6 | Intravascular ultrasound radiofrequeney analysis of coronary atherosclerosis:an emerging technology for the assessment of vulnerable plaque显示文摘 | Mehta S K McCrary J R Frutkin A D | 2007 | European Heart Journal2007，28，11： | 1 |
| 7 | Effect of compressed CO2 on crystallization and melting behavior of isotactic polyproplene显示文摘 | Varma-Nair M Handa P Y Mehta A K | 2003 | ThermochimicaActa2003，396，： | 1 |
| 8 | Quantification of sub-femtomole amounts of Alzheimer amyloid beta peptides显示文摘 | Potempska A Mack K Mehta P | 1999 | Amyloid1999，6，1： | 1 |
| 9 | Development of a feature recognition module for tapered and curved base featores显示文摘 | Arivazhagan A Mehta N K Jain P K | 2008 | Int J Adv Manuf Technol2008，39，： | 1 |
| 10 | Simple estimation of prevalence of Hortonian flow in New York City Watershed显示文摘 | Walter M T V K Mehta A M Marrone J | 2003 | Journal of Hydrology Engineering2003，，8： | 1 |
| 11 | The antimicrobial effi ciency of root oil against human pathogenic bacteria and phy topatbogenic fungi显示文摘 | Jaiswal K S Batra K A Mehta B K | 1984 | Phytopathol Z1984，109，1： | 1 |
| 12 | Eukaryotic translation initia- tion factors in cancer development and progression 显示文摘 | Spilka R Ernst C Mehta A K | 2013 | Cancer Lett2013，340，1： | 1 |
| 13 | Acute kidney iniury global health alert显示文摘 | LIP K BURDMANN E A MEHTA R L | 2013 | Kidney Int2013，83，3： | 1 |
| 14 | Innate signals from Nod2 block respiralory toler ance and program T(H)2-driven allergic inflammation 显示文摘 | DUAN W MEHTA A K MAGALHAES J G | 2010 | J AllergyClinlmmunol2010，126，： | 1 |
| 15 | Development of a feature recognition module for tapered and curved base features显示文摘 | Arivazhagan A Mehta N K Jain P K | 2008 | Int J Adv Manuf Technol2008，39，： | 1 |
| 16 | Routine vs selective invasive strategies in patients with acute coro- nary syndromes: a collaborative recta-analysis of rando- mized trials 显示文摘 | Mehta S R Cannon C P Fox K A | 2005 | JAMA2005，293，23： | 1 |
| 17 | Rapid diagnosis of extensively drug-resistant tuberculosis by use of a reverse line blot hybridization assay显示文摘 | Ajbani K Shetty A Mehta A | 2011 | J Clin Microbiol2011，49，7： | 1 |
| 18 | Post-lung transplantation Aspergillus niger infection显示文摘 | Singhal P Usuda K Mehta A C | 2005 | J Heart Lung Transplant2005，24，： | 1 |
| 19 | A computational approach to infemng cellular protein-binding affinities from quantitative fluorescence resonance energy transfer imaging显示文摘 | Mehta K Hoppe A D Kainkaryam R Woolf P J Linderman J J | | 0，，23： | 1 |
| 20 | Adverse impact of bleeding on prognosis in patients with acute coronary syndromes显示文摘 | Eikelboom J W Mehta S R Anand S S Xie C Fox K A Yusuf S | 2006 | Circulation2006，114，： | 1 |
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