Demethylation restores SN38 sensitivity in cells with acquired resistance to SN38 derived from human cervical squamous cancer cells

  • Authors:
    • Tetsuji Tanaka
    • Tao Bai
    • Saori Toujima
    • Tomoko Utsunomiya
    • Toshihide Matsuoka
    • Aya Kobayashi
    • Madoka Yamamoto
    • Noriyuki Sasaki
    • Yuko Tanizaki
    • Hirotoshi Utsunomiya
    • Junko Tanaka
    • Kazunori Yukawa
  • View Affiliations

  • Published online on: January 11, 2012     https://doi.org/10.3892/or.2012.1628
  • Pages: 1292-1298
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Abstract

Using seven monoclonal SN38-resistant subclones established from ME180 human cervical squamous cell carcinoma cells, we examined the demethylation effects of 5-aza-2'-deoxycytidine (5-aza-CdR) on the SN38-sensitivity of the cells as well as the expression of death-associated protein kinase (DAPK) in the SN38-resistant cells. The DAPK expression levels were evaluated among parent ME180 cells, SN38-resistant ME180 cells and cisplatin-resistant ME180 cells by methylation-specific DAPK-PCR, quantitative RT-PCR and western blot analysis. The SN38-resistant cells co-treated with SN38 and 5-aza-CdR strongly exhibited enhanced SN38-sensitivities resembling those found in the parent cells. In the SN38-resistant subclones, no relationships were found between the restored SN38 sensitivity and hypermethylation of the DAPK promoter, DAPK mRNA expression, DAPK protein expression and induction of DAPK protein after 5-aza-CdR treatment, unlike the strong suppression of 5-aza-CdR-induced DAPK protein expression in the cisplatin-resistant subclones. These findings indicate that reversibly methylated molecules, but not DAPK, may regulate SN38 resistance, and that demethylating agents can be strong sensitizing anticancer chemotherapeutic drugs for SN38-resistant cancers.

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April 2012
Volume 27 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Tanaka T, Bai T, Toujima S, Utsunomiya T, Matsuoka T, Kobayashi A, Yamamoto M, Sasaki N, Tanizaki Y, Utsunomiya H, Utsunomiya H, et al: Demethylation restores SN38 sensitivity in cells with acquired resistance to SN38 derived from human cervical squamous cancer cells. Oncol Rep 27: 1292-1298, 2012.
APA
Tanaka, T., Bai, T., Toujima, S., Utsunomiya, T., Matsuoka, T., Kobayashi, A. ... Yukawa, K. (2012). Demethylation restores SN38 sensitivity in cells with acquired resistance to SN38 derived from human cervical squamous cancer cells. Oncology Reports, 27, 1292-1298. https://doi.org/10.3892/or.2012.1628
MLA
Tanaka, T., Bai, T., Toujima, S., Utsunomiya, T., Matsuoka, T., Kobayashi, A., Yamamoto, M., Sasaki, N., Tanizaki, Y., Utsunomiya, H., Tanaka, J., Yukawa, K."Demethylation restores SN38 sensitivity in cells with acquired resistance to SN38 derived from human cervical squamous cancer cells". Oncology Reports 27.4 (2012): 1292-1298.
Chicago
Tanaka, T., Bai, T., Toujima, S., Utsunomiya, T., Matsuoka, T., Kobayashi, A., Yamamoto, M., Sasaki, N., Tanizaki, Y., Utsunomiya, H., Tanaka, J., Yukawa, K."Demethylation restores SN38 sensitivity in cells with acquired resistance to SN38 derived from human cervical squamous cancer cells". Oncology Reports 27, no. 4 (2012): 1292-1298. https://doi.org/10.3892/or.2012.1628