Abstract
Two 5-fluorouracil (5-FU)-resistant cell lines from a Korean gastric cancer cell line were established by incubation of the cells with increasing concentration of 5-FU, and the resultant cell lines showed an over 800-fold increased resistance to 5-FU. To identify the mechanism of 5-FU resistance, the expressions of genes involved in 5-FU metabolism were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Expressions of orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and uridine phosphorylase (UP) were significantly downregulated in these cell lines, resulting in low incorporation of 5-FU into nucleic acids. In contrast, an increased expression of thymidine kinase (TK) was observed in 5-FU-resistant cells. These results strongly indicate that blocking of 5-FU incorporation into nucleic acids and TK overexpression may play a major role in 5-FU resistance in these cells. Interestingly, these cell lines showed cross- resistance to paclitaxel, cisplatin, and doxorubicin, suggesting that other factors such as HSP27 and Mn-SOD could be also involved in the mechanism of multidrug resistance in these cell lines. (C) 2000 Elsevier Science Ireland Ltd.
Original language | English |
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Pages (from-to) | 95-101 |
Number of pages | 7 |
Journal | Cancer letters |
Volume | 159 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2000 Oct 16 |
Keywords
- 5-Fluorouracil
- 5-Fluorouracil-anabolizing enzymes
- Cross-resistance
- Multidrug resistance
ASJC Scopus subject areas
- Oncology
- Cancer Research