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Article

Establishment of 5-fluorouracil-resistant oral squamous cell carcinoma cell lines with epithelial to mesenchymal transition changes

  • Authors:
    • Koji Harada
    • Tarannum Ferdous
    • Yoshiya Ueyama
  • View Affiliations / Copyright

    Affiliations: Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
  • Pages: 1302-1308
    |
    Published online on: January 21, 2014
       https://doi.org/10.3892/ijo.2014.2270
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Abstract

5-Fluorouracil (5-FU) has been used for oral squamous cell carcinoma (OSCC) treatments, and the acquisition of resistance is the major problem to successful OSCC treatment. It has been reported that the epithelial to mesenchymal transition (EMT) is associated with chemoresistance in several types of cancers. In the present study, we established 5-FU-resistant OSCC cell lines (HSC2/FU and HSC4/FU), and aimed to elucidate the mechanism(s) involved in resistance in association with its EMT characteristics. MTT assay revealed that HSC2/FU is about 14-fold more resistant compared to HSC2, and HSC4/FU is 5-fold more resistant compared to HSC4. TUNEL assay also showed a dramatically decreased number of apoptotic cells in the 5-FU-resistant OSCC cell lines compared to each parental cell after treatment with 5-FU. Moreover, the 5-FU-resistant OSCC cell lines had typical morphologic phenotypes of EMT; loss of cell-cell adhesion, increased formation of pseudopodia and spindle-shaped morphology. Western blot analysis showed downregulated E-cadherin, and upregulated N-cadherin and Twist in the 5-FU-resistant OSCC cell lines. Results of our tumor xenograft studies coincide with our in vitro study data that confirmed the 5-FU resistant nature of HSC2/FU and HSC4/FU tumors. Moreover, immunohistochemistry showed that EMT changes (downregulated E-cadherin, and upregulated Twist and N-cadherin) occurred in the 5-FU-resistant xenografted tumor cells. These results suggest that EMT has important roles in the 5-FU-resistant OSCC cells, and that these resistant cells may be considered as useful tools for understanding the mechanisms involved in 5-FU resistance in OSCC.
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Copy and paste a formatted citation
Spandidos Publications style
Harada K, Ferdous T and Ueyama Y: Establishment of 5-fluorouracil-resistant oral squamous cell carcinoma cell lines with epithelial to mesenchymal transition changes. Int J Oncol 44: 1302-1308, 2014.
APA
Harada, K., Ferdous, T., & Ueyama, Y. (2014). Establishment of 5-fluorouracil-resistant oral squamous cell carcinoma cell lines with epithelial to mesenchymal transition changes. International Journal of Oncology, 44, 1302-1308. https://doi.org/10.3892/ijo.2014.2270
MLA
Harada, K., Ferdous, T., Ueyama, Y."Establishment of 5-fluorouracil-resistant oral squamous cell carcinoma cell lines with epithelial to mesenchymal transition changes". International Journal of Oncology 44.4 (2014): 1302-1308.
Chicago
Harada, K., Ferdous, T., Ueyama, Y."Establishment of 5-fluorouracil-resistant oral squamous cell carcinoma cell lines with epithelial to mesenchymal transition changes". International Journal of Oncology 44, no. 4 (2014): 1302-1308. https://doi.org/10.3892/ijo.2014.2270
Copy and paste a formatted citation
x
Spandidos Publications style
Harada K, Ferdous T and Ueyama Y: Establishment of 5-fluorouracil-resistant oral squamous cell carcinoma cell lines with epithelial to mesenchymal transition changes. Int J Oncol 44: 1302-1308, 2014.
APA
Harada, K., Ferdous, T., & Ueyama, Y. (2014). Establishment of 5-fluorouracil-resistant oral squamous cell carcinoma cell lines with epithelial to mesenchymal transition changes. International Journal of Oncology, 44, 1302-1308. https://doi.org/10.3892/ijo.2014.2270
MLA
Harada, K., Ferdous, T., Ueyama, Y."Establishment of 5-fluorouracil-resistant oral squamous cell carcinoma cell lines with epithelial to mesenchymal transition changes". International Journal of Oncology 44.4 (2014): 1302-1308.
Chicago
Harada, K., Ferdous, T., Ueyama, Y."Establishment of 5-fluorouracil-resistant oral squamous cell carcinoma cell lines with epithelial to mesenchymal transition changes". International Journal of Oncology 44, no. 4 (2014): 1302-1308. https://doi.org/10.3892/ijo.2014.2270
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