Establishment and characterization of two 5-fluorouracil-resistant hepatocellular carcinoma cell lines

  • Authors:
    • Kazuya Uchibori
    • Atsushi Kasamatsu
    • Masahiko Sunaga
    • Satoshi  Yokota
    • Tomoya Sakurada
    • Eriko Kobayashi
    • Masaharu Yoshikawa
    • Katsuhiro  Uzawa
    • Shiro Ueda
    • Hideki Tanzawa
    • Nobunori Sato
  • View Affiliations

  • Published online on: December 15, 2011     https://doi.org/10.3892/ijo.2011.1300
  • Pages: 1005-1010
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Abstract

5-Fluorouracil (5-FU) chemotherapy is the first choice treatment for advanced hepatocellular carcinoma (HCC), and resistance is the major obstacle to successful treatment. Recent studies have reported that epithelial-to-mesenchymal transition (EMT) is associated with chemoresistance in cancers. We speculated that EMT and 5-FU metabolism are related to the mechanism of 5-FU resistance. First, two 5-FU-resistant cell lines, HLF-R4 and HLF-R10, were established from the HLF undifferentiated human HCC cell line. Whereas cell growth was similar in the HLF and HLF-R cell lines, HLF-Rs are about 4- and 10-fold more resistant compared with the HLF cells; thus, we named these cell lines HLF-R4 and HLF-R10, respectively. The terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling assay also showed a dramatically decreased number of apoptotic cells in the HLF-Rs after treatment with 5-FU. We next assessed the characteristics of the HLF, HLF-R4 and HLF-R10 cells. Consistent with our hypothesis, the HLF-Rs had typical morphologic phenotypes of EMT, loss of cell-cell adhesion, spindle-shaped morphology and increased formation of pseudopodia. Real-time quantitative reverse transcriptase polymerase chain reaction data showed downregulated E-cadherin and upregulated Twist-1 and also indicated that EMT changes occurred in the HLF-Rs. We also found decreased ribonucleotide reductase and increased multidrug resistance protein 5 genes in the HLF-R cells. Our results suggested that the metabolism of EMT and 5-FU has important roles in 5-FU chemoresistance in the HLF-R cells, and that the HLF-R cells would be useful in vitro models for understanding the 5-FU-resistant mechanisms in HCC.
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April 2012
Volume 40 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Uchibori K, Kasamatsu A, Sunaga M, Yokota S, Sakurada T, Kobayashi E, Yoshikawa M, Uzawa K, Ueda S, Tanzawa H, Tanzawa H, et al: Establishment and characterization of two 5-fluorouracil-resistant hepatocellular carcinoma cell lines. Int J Oncol 40: 1005-1010, 2012
APA
Uchibori, K., Kasamatsu, A., Sunaga, M., Yokota, S., Sakurada, T., Kobayashi, E. ... Sato, N. (2012). Establishment and characterization of two 5-fluorouracil-resistant hepatocellular carcinoma cell lines. International Journal of Oncology, 40, 1005-1010. https://doi.org/10.3892/ijo.2011.1300
MLA
Uchibori, K., Kasamatsu, A., Sunaga, M., Yokota, S., Sakurada, T., Kobayashi, E., Yoshikawa, M., Uzawa, K., Ueda, S., Tanzawa, H., Sato, N."Establishment and characterization of two 5-fluorouracil-resistant hepatocellular carcinoma cell lines". International Journal of Oncology 40.4 (2012): 1005-1010.
Chicago
Uchibori, K., Kasamatsu, A., Sunaga, M., Yokota, S., Sakurada, T., Kobayashi, E., Yoshikawa, M., Uzawa, K., Ueda, S., Tanzawa, H., Sato, N."Establishment and characterization of two 5-fluorouracil-resistant hepatocellular carcinoma cell lines". International Journal of Oncology 40, no. 4 (2012): 1005-1010. https://doi.org/10.3892/ijo.2011.1300