| Summary: | 碩士 === 高雄醫學大學 === 醫學研究所 === 98 === 5-fluorouracil (5-FU) has been used for decades to treat various types of malignancies, including colon, breast, bladder, head and neck, and liver cancers. However, its efficacy is frequently reduced by acquisition of drug resistance in cancer cells. This study focuses on examining the hypothesis that DNA repair activity may be altered when the tumor cells acquire drug resistance. First, the 5-FU-resistant laryngeal (H-F5 and H-F10) and oral (Ca-F1, Ca-F2.5) cancer cell lines were established by long-term growing the HEp-2 and Ca9-22 cells, respectively, in various concentrations of 5-FU. The IC50 (50% growth inhibitory concentration) of these cells were HEp-2: 19.1 μM, H-F5: 22.1 μM, H-F10: 48.9 μM, Ca9-22: 8.1 μM, Ca-F1: 10.2 μM, Ca-F2.5: 9.9 μM. Next, nucleotide excision repair (NER), homologous recombination repair (HRR), and non-homologous end-joining (NHEJ) repair analyses were performed. The results showed that the NER activities of H-F10 and Ca-F1 were 1.4-fold and 3.2-fold higher than those of HEp-2 and Ca9-22, respectively. No apparent change of NER activity was found between H-F5 and HEp-2. For HRR and NHEJ repair, all cell lines exhibited similar activities between drug-resistant and parental cells, except for Ca-F1 whose NHEJ repair activity was lower than Ca9-22. By western blot analyses, we found that RPA and DDB1 had increased in H-F10, and XPA, ERCC1, and DDB1 had increased in Ca-F1 cells.This results suggested that cells acquired 5-FU resistance might also alter NER activites.
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