Antisense Bcl-2 and HER-2 oligonucleotide treatment of breast cancer cells enhances their sensitivity to anticancer drugs

  • Authors:
    • Kazuaki Tanabe
    • Ryungsa Kim
    • Hideki Inoue
    • Manabu Emi
    • Yoko Uchida
    • Tetsuya Toge
  • View Affiliations

  • Published online on: April 1, 2003     https://doi.org/10.3892/ijo.22.4.875
  • Pages: 875-881
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Abstract

Overexpression of the HER-2 correlates with drug-resistance and a poor prognosis in breast cancer, however the mechanism(s) of HER-2-mediated drug-resistance are unknown. We examined the effects of antisense Bcl-2 and HER-2 oligonucleotides (ODN) to assess the mechanism(s) through which down-regulation of Bcl-2 and HER-2 enhances drug-sensitivity. Using two human breast cancer cell lines, MDA-MB-231 and BT-474, the antitumor effects of a combination of antisense ODN and anticancer drugs, including mitomycin C (MMC), adriamycin (ADM), paclitaxel (TXL), and docetaxel (TXT) was evaluated. The expression of Bcl-2 protein was suppressed by treatment with antisense Bcl-2 ODN in a dose-dependent manner. An enhanced drug-sensitivity to MMC and TXL upon pretreatment with antisense Bcl-2 ODN was observed, with the IC50 values increasing 1.9- and 2.0-fold, respectively. Treatment of BT-474 cells with antisense HER-2 at 1.0 µM suppressed HER-2 overexpression by 60.5%. Pretreatment with antisense HER-2 ODN increased the sensitivity of these cells to ADM and TXL 20.8- and 10.8-fold, respectively. In vivo experiments using a combination of antisense HER-2 and TXL showed the similar enhancement of antitumor effect of TXL as compared to that of antisense HER-2 or TXL alone (p=0.068). Enhancement of drug-sensitivity was associated with the induction of apoptosis. Of interest, treatment with antisense HER-2 ODN also suppressed the expression of Bcl-2 and pAkt. These results indicate that down-regulation of Bcl-2 and HER-2 increased drug-sensitivity by modulating drug-induced apoptotic pathways in breast cancer cells, and that antisense ODN therapy, targeting Bcl-2 and HER-2 may be a useful strategy to enhance drug-sensitivity.

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April 2003
Volume 22 Issue 4

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

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Spandidos Publications style
Tanabe K, Kim R, Inoue H, Emi M, Uchida Y and Toge T: Antisense Bcl-2 and HER-2 oligonucleotide treatment of breast cancer cells enhances their sensitivity to anticancer drugs. Int J Oncol 22: 875-881, 2003
APA
Tanabe, K., Kim, R., Inoue, H., Emi, M., Uchida, Y., & Toge, T. (2003). Antisense Bcl-2 and HER-2 oligonucleotide treatment of breast cancer cells enhances their sensitivity to anticancer drugs. International Journal of Oncology, 22, 875-881. https://doi.org/10.3892/ijo.22.4.875
MLA
Tanabe, K., Kim, R., Inoue, H., Emi, M., Uchida, Y., Toge, T."Antisense Bcl-2 and HER-2 oligonucleotide treatment of breast cancer cells enhances their sensitivity to anticancer drugs". International Journal of Oncology 22.4 (2003): 875-881.
Chicago
Tanabe, K., Kim, R., Inoue, H., Emi, M., Uchida, Y., Toge, T."Antisense Bcl-2 and HER-2 oligonucleotide treatment of breast cancer cells enhances their sensitivity to anticancer drugs". International Journal of Oncology 22, no. 4 (2003): 875-881. https://doi.org/10.3892/ijo.22.4.875