Alterations of DNA repair activities in 5-fluorouracil-resistant oral cancer cell lines
碩士 === 高雄醫學大學 === 醫學研究所 === 98 === 5-fluorouracil (5-FU) is widely used for treatment of many types of cancers, including oral cancer. However, 5-FU resistance often leads to treatment failure and recurrence. The exact molecular mechanisms of 5-FU resistance have not been fully elucidated. The purpo...
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ndltd-TW-098KMC055340522016-04-18T04:21:00Z http://ndltd.ncl.edu.tw/handle/52325581121927623783 Alterations of DNA repair activities in 5-fluorouracil-resistant oral cancer cell lines 探討具5-fluorouracil抗性之口腔癌細胞株的DNA修補能力 Huei-Yu Tsai 蔡蕙瑜 碩士 高雄醫學大學 醫學研究所 98 5-fluorouracil (5-FU) is widely used for treatment of many types of cancers, including oral cancer. However, 5-FU resistance often leads to treatment failure and recurrence. The exact molecular mechanisms of 5-FU resistance have not been fully elucidated. The purpose of this study is to explore the role of DNA repair in 5-FU-resistant oral cancer cell lines. The 5-FU-resistant KB (KB-F5, KB-F10) and SAS (SAS-F1) cell lines were established after a long-term treatment of 5-FU, and were examined for their DNA repair activities. The results showed that nucleotide excision repair (NER) was repressed in 5-FU-resistant cell lines; homologous recombination repair (HRR) was activated in KB-F5 and KB-F10, but not in SAS-F1 when compared with the parental cells. The repair activity via non-homologous end joining (NHEJ) was higher in SAS-F1 than that in parental SAS cells. No significant difference in NHEJ repair could be found between KB and their 5-FU-resistant clones. The expressions of DNA repair genes were examined by western blots. The results showed that p53 was increased in the resistant cells. Previous studies have indicated that loss of p53 activity may lead to 5-FU drug resistance. Indeed, we found that the p53 transcriptional activity was decreased in the resistant cells. These findings suggested that NER activity was decreased in 5-FU resistant KB and SAS cell lines. However, KB-F5 and KB-F10 might acquire 5-FU resistance by elevating HRR activity, while 5-FU resistance of SAS-F1 might be due to the increased NHEJ repair. Chang-Shen Lin 林常申 2010 學位論文 ; thesis 85 zh-TW |
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碩士 === 高雄醫學大學 === 醫學研究所 === 98 === 5-fluorouracil (5-FU) is widely used for treatment of many types of cancers, including oral cancer. However, 5-FU resistance often leads to treatment failure and recurrence. The exact molecular mechanisms of 5-FU resistance have not been fully elucidated. The purpose of this study is to explore the role of DNA repair in 5-FU-resistant oral cancer cell lines. The 5-FU-resistant KB (KB-F5, KB-F10) and SAS (SAS-F1) cell lines were established after a long-term treatment of 5-FU, and were examined for their DNA repair activities. The results showed that nucleotide excision repair (NER) was repressed in 5-FU-resistant cell lines; homologous recombination repair (HRR) was activated in KB-F5 and KB-F10, but not in SAS-F1 when compared with the parental cells. The repair activity via non-homologous end joining (NHEJ) was higher in SAS-F1 than that in parental SAS cells. No significant difference in NHEJ repair could be found between KB and their 5-FU-resistant clones. The expressions of DNA repair genes were examined by western blots. The results showed that p53 was increased in the resistant cells. Previous studies have indicated that loss of p53 activity may lead to 5-FU drug resistance. Indeed, we found that the p53 transcriptional activity was decreased in the resistant cells. These findings suggested that NER activity was decreased in 5-FU resistant KB and SAS cell lines. However, KB-F5 and KB-F10 might acquire 5-FU resistance by elevating HRR activity, while 5-FU resistance of SAS-F1 might be due to the increased NHEJ repair.
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author2 |
Chang-Shen Lin |
author_facet |
Chang-Shen Lin Huei-Yu Tsai 蔡蕙瑜 |
author |
Huei-Yu Tsai 蔡蕙瑜 |
spellingShingle |
Huei-Yu Tsai 蔡蕙瑜 Alterations of DNA repair activities in 5-fluorouracil-resistant oral cancer cell lines |
author_sort |
Huei-Yu Tsai |
title |
Alterations of DNA repair activities in 5-fluorouracil-resistant oral cancer cell lines |
title_short |
Alterations of DNA repair activities in 5-fluorouracil-resistant oral cancer cell lines |
title_full |
Alterations of DNA repair activities in 5-fluorouracil-resistant oral cancer cell lines |
title_fullStr |
Alterations of DNA repair activities in 5-fluorouracil-resistant oral cancer cell lines |
title_full_unstemmed |
Alterations of DNA repair activities in 5-fluorouracil-resistant oral cancer cell lines |
title_sort |
alterations of dna repair activities in 5-fluorouracil-resistant oral cancer cell lines |
publishDate |
2010 |
url |
http://ndltd.ncl.edu.tw/handle/52325581121927623783 |
work_keys_str_mv |
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