Establishment and characterization of 5-fluorouracil-resistant gastric cancer cells

Young Min Chung, Sun Hee Park., Jong Kuk Park, Yoon Taik Kim, Yoon Koo Kang, Young Do Yoo

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)95-101
Number of pages7
JournalCancer Letters
Volume159
Issue number1
DOIs
Publication statusPublished - 2000 Oct 16
Externally publishedYes

Fingerprint

Fluorouracil
Stomach Neoplasms
Cells
Cell Line
Thymidine Kinase
Nucleic Acids
Orotate Phosphoribosyltransferase
Uridine Phosphorylase
Thymidine Phosphorylase
Polymerase chain reaction
RNA-Directed DNA Polymerase
Multiple Drug Resistance
Paclitaxel
Reverse Transcriptase Polymerase Chain Reaction
Metabolism
Doxorubicin
Cisplatin
Superoxide Dismutase
Down-Regulation
Genes

Keywords

  • 5-Fluorouracil
  • 5-Fluorouracil-anabolizing enzymes
  • Cross-resistance
  • Multidrug resistance

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

Establishment and characterization of 5-fluorouracil-resistant gastric cancer cells. / Chung, Young Min; Park., Sun Hee; Park, Jong Kuk; Kim, Yoon Taik; Kang, Yoon Koo; Yoo, Young Do.

In: Cancer Letters, Vol. 159, No. 1, 16.10.2000, p. 95-101.

Research output: Contribution to journalArticle

Chung, Young Min ; Park., Sun Hee ; Park, Jong Kuk ; Kim, Yoon Taik ; Kang, Yoon Koo ; Yoo, Young Do. / Establishment and characterization of 5-fluorouracil-resistant gastric cancer cells. In: Cancer Letters. 2000 ; Vol. 159, No. 1. pp. 95-101.
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