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http://140.128.103.80:8080/handle/310901/23251
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| Title: | Rosiglitazone enhances the radiosensitivity of p53-mutant HT-29 human colorectal cancer cells |
| Authors: | Chiu, S.-J.ab , Hsaio, C.-H.a, Tseng, H.-H.a, Su, Y.-H.a, Shih, W.-L.c, Lee, J.-W.a, Chuah, J.Q.-Y.a |
| Contributors: | Department of Life Science, Tunghai University |
| Keywords: | Human colorectal cancer cells;Radiosensitivity;Rosiglitazone |
| Date: | 2010 |
| Issue Date: | 2013-06-11T09:05:00Z (UTC)
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| Abstract: | Combined-modality treatment has improved the outcome in cases of various solid tumors, and radiosensitizers are used to enhance the radiotherapeutic efficiency. Rosiglitazone, a synthetic ligand of peroxisome proliferator-activated receptors γ used in the treatment of type-2 diabetes, has been shown to reduce tumor growth and metastasis in human cancer cells, and may have the potential to be used as a radiosensitizer in radiotherapy for human colorectal cancer cells. In this study, rosiglitazone treatment significantly reduced the cell viability of p53-wild type HCT116 cells but not p53-mutant HT-29 cells. Interestingly, rosiglitazone pretreatment enhanced radiosensitivity in p53-mutant HT-29 cells but not HCT116 cells, and prolonged radiation-induced G 2/M arrest and enhanced radiation-induced cell growth inhibition in HT-29 cells. Pretreatment with rosiglitazone also suppressed radiation-induced H2AX phosphorylation in response to DNA damage and AKT activation for cell survival; on the contrary, rosiglitazone pretreatment enhanced radiation-induced caspase-8, -9, and -3 activation and PARP cleavage in HT-29 cells. In addition, pretreatment with a pan-caspase inhibitor, zVAD-fmk, attenuated the levels of caspase-3 activation and PARP cleavage in radiation-exposed cancer cells in combination with rosiglitazone pretreatment. Our results provide proof for the first time that rosiglitazone suppresses radiation-induced survival signals and DNA damage response, and enhances the radiation-induced apoptosis signaling cascade. These findings can assist in the development of rosiglitazone as a novel radiosensitizer. ? 2010 Elsevier Inc. All rights reserved. |
| Relation: | Biochemical and Biophysical Research Communications
Volume 394, Issue 3, 9 April 2010, Pages 774-779 |
| Appears in Collections: | [生命科學系所] 期刊論文
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