Reversal of drug resistance using hammerhead ribozymes against multidrug resistance-associated protein and multidrug resistance 1 gene

  • Authors:
    • Junko Nagata
    • Hiroshi Kijima
    • Hiroyuki Hatanaka
    • Satomi Asai
    • Hayato Miyachi
    • Yoshiyuki Abe
    • Hitoshi Yamazaki
    • Masato Nakamura
    • Norihito Watanabe
    • Tetsuya Mine
    • Takahito Kondo
    • Kevin J. Scanlon
    • Yoshito Ueyama
  • View Affiliations

  • Published online on: November 1, 2002     https://doi.org/10.3892/ijo.21.5.1021
  • Pages: 1021-1026
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Abstract

We examined the effects of suppressing multidrug resistance-associated protein (MRP) and multidrug resistance 1 (MDR1) gene expression in HCT-8DDP human colon cancer cell lines, which showed both cisplatin and multidrug resistance. Hammerhead ribozymes, designed to cleave MRP mRNA (anti-MRP Rz) and MDR1 mRNA (anti-MDR1 Rz), were transfected into the HCT-8DDP cells. Drug sensitivity was estimated by MTT assay in vitro. The HCT-8DDP/anti-MRP Rz cells were more sensitive to doxorubicin (DOX) and etoposide (VP-16) by 2.5- and 4.1-fold, respectively, compared with HCT-8DDP cells. The HCT-8DDP/anti-MDR Rz cells were more sensitive to DOX and VP-16 by 2.3- and 3.8-fold, respectively. The anti-MRP Rz and anti-MDR1 Rz significantly down-regulated resistance to DOX and VP-16, while anti-MRP Rz and anti-MDR1 Rz did not affect resistance to cisplatin, methotrexate and 5-fluorouracil. The hammerhead ribozyme-mediated specific suppression of MRP or MDR1 was sufficient to reverse multidrug resistance in the human colon cancer cell line.

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November 2002
Volume 21 Issue 5

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

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Spandidos Publications style
Nagata J, Kijima H, Hatanaka H, Asai S, Miyachi H, Abe Y, Yamazaki H, Nakamura M, Watanabe N, Mine T, Mine T, et al: Reversal of drug resistance using hammerhead ribozymes against multidrug resistance-associated protein and multidrug resistance 1 gene. Int J Oncol 21: 1021-1026, 2002
APA
Nagata, J., Kijima, H., Hatanaka, H., Asai, S., Miyachi, H., Abe, Y. ... Ueyama, Y. (2002). Reversal of drug resistance using hammerhead ribozymes against multidrug resistance-associated protein and multidrug resistance 1 gene. International Journal of Oncology, 21, 1021-1026. https://doi.org/10.3892/ijo.21.5.1021
MLA
Nagata, J., Kijima, H., Hatanaka, H., Asai, S., Miyachi, H., Abe, Y., Yamazaki, H., Nakamura, M., Watanabe, N., Mine, T., Kondo, T., Scanlon, K. J., Ueyama, Y."Reversal of drug resistance using hammerhead ribozymes against multidrug resistance-associated protein and multidrug resistance 1 gene". International Journal of Oncology 21.5 (2002): 1021-1026.
Chicago
Nagata, J., Kijima, H., Hatanaka, H., Asai, S., Miyachi, H., Abe, Y., Yamazaki, H., Nakamura, M., Watanabe, N., Mine, T., Kondo, T., Scanlon, K. J., Ueyama, Y."Reversal of drug resistance using hammerhead ribozymes against multidrug resistance-associated protein and multidrug resistance 1 gene". International Journal of Oncology 21, no. 5 (2002): 1021-1026. https://doi.org/10.3892/ijo.21.5.1021