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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 | Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer显示文摘 | Haffty BG Yang Q Reiss M | 2006 | J Clin Oncol2006，24，36： | 1 |
| 3 | Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer 显示文摘 | Haffty B G Yang Q Reiss M | 2006 | J Clin Oncol2006，24，： | 1 |
| 4 | Intraoperative brachytherapy, and gastrict transposition for patients with recurrent hypopharyngeal and cervical esophageal carcinoma显示文摘 | Wilson LD Chung JY Haffty BG | 1998 | Laryngoscope1998，108，10： | 1 |
| 5 | Ductal carcino- ma in situ with microinvasion : prognostic implications, long - term outcomes, and role of axillary evaluation 显示文摘 | PARIKH R R HAFFTY B G LANNIN D et at | 2012 | Int J Radiat Oncol Biol Phys2012，82，1： | 1 |
| 6 | Ipsilateral breast tumor recurrence as a predictor of distant disease:implications for systemic therapy at the time of local relapse显示文摘 | Reiss M Beinfield M | 1996 | J Clin Oncol1996，14，： | 1 |
| 7 | ACR appropri- ateness criteria on postmastectomy radiotherapy expert panel on radiation oncology-breast 显示文摘 | Taylor ME Haffty BG Rabinovitch R | 2009 | Int J Radiat Oncol Biol Phys2009，73，4： | 1 |
| 8 | Using respiratory motion toguide planning target volume margins for external beam partialbreast irradiation显示文摘 | Kim LH Goyal S Haffty BG | 2012 | Int J Radiat Oncol Biol Phys2012，82，4： | 1 |
| 9 | Local-regional breast cancer recurrence: prognostic groups based on patterns of failure 显示文摘 | MORAN MS HAFFTY BG | 2002 | Breast J2002，8，2： | 1 |
| 10 | Locoregional relapse and distant metastasis in conservatively managed triple negative early stage breast cancer 显示文摘 | Haffty BG Yang Q Reiss M | 2006 | J Clin Oncol2006，24，36： | 1 |
| 11 | Estrogen dependent prognostic significance of cyclooxygenase-2 expression in early-stage invasive breast cancers treated with breast conserving surgery and radiation显示文摘 | Haffty BG Yang Q Moran MS | 2008 | Int J Radiat Oncol Biol Phys2008，71，4： | 1 |
| 12 | Locoregional relapse and distant metastasis in conservatively managed triple negative early stage breast cancer显示文摘 | Haffty BG Yang Q Reiss M | 2006 | J Clin Oncol2006，24，： | 1 |
| 13 | Local-regional breast cancer recurrence: prognostic groups based on patterns of failure 显示文摘 | Moran MS Haffty BG | 2002 | Breast J2002，8，2： | 1 |
| 14 | Carcinoma of the larynx treated with hypofractionated radiation and hyperbaric oxygen:long-term tumor control and complications显示文摘 | Haffty BG Hurley RA Peters LG | 1999 | Int J Radiation Oncology Biol Phys1999，45，1： | 1 |
| 15 | Locoregional relapse and distant metastasis in conservatively managed triple negative earlystage breast cancer显示文摘 | Haffty BG Yang Q Reiss M | 2006 | J Clin Oncol2006，24，36： | 1 |
| 16 | Positive sentinel nodes without axillary dissection: implications for the radiation oncologist显示文摘 | Haffty BG Hunt KK Harris JR | 2011 | J C lin Oncol2011，29，34： | 1 |
| 17 | Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer显示文摘 | Haffty B G Yang Q Reiss M | 2006 | J Clin Oncol2006，24，36： | 1 |
| 18 | Local recurrence of breast cancer after breast conservation therapy in patients examined by means of stereotactic core-needle biopsy显示文摘 | Chen A M Haffty B G Lee C H | 2002 | Radiology2002，225，3： | 1 |
| 19 | Low p53 binding protein1 (53BP1 ) expression is associated with increased local recur-rence in breast cancer patients treated with breast - conservingsurgery and radiotherapy显示文摘 | Neboori HJ Haffty BG Wu H | 2012 | Int J Radiat Oncol Biol Phys2012，83，5： | 1 |
| 20 | Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast eancer显示文摘 | Haffty BG Yang Q Reiss M ctal | 2006 | J ClinOncol2006，24，36： | 1 |
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