Inhibition of MMP-9 using a pyrrole-imidazole polyamide reduces cell invasion in renal cell carcinoma

  • Authors:
    • Aya Sato
    • Hiroki Nagase
    • Daisuke Obinata
    • Kyoko Fujiwara
    • Noboru Fukuda
    • Masayoshi Soma
    • Kenya Yamaguchi
    • Nozomu Kawata
    • Satoru Takahashi
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  • Published online on: August 21, 2013     https://doi.org/10.3892/ijo.2013.2073
  • Pages: 1441-1446
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Abstract

We investigated the clinical significance of the expression levels of matrix metalloproteinase 9 (MMP-9) in renal cell carcinoma (RCC). In addition, we validated the efficacy of pyrrole imidazole polyamide (PIP) targeting MMP-9 on inhibiting proliferation and invasion of RCC. We evaluated the expression levels of MMP-9 in 249 RCC specimens by immunostaining and analyzed the association between MMP-9 expression levels and cancer-specific survival. Furthermore, in a human RCC cell line, Caki-2, we tested the effect of a couple of PIPs targeting MMP-9 one recognizing an NF-κB binding site (MMP-9-NF-κB PIP) and another for the AP-1 binding site (MMP-9-AP-1 PIP) in the MMP-9 promoter. The expression levels of MMP-9, proliferative activity and invasive capability were tested by quantitative PCR, WST8 assay and Matrigel invasion assay, respectively. By immunostaining of the clinical specimens, strong MMP-9 staining was proven to be a significant predictor of poor prognosis for cancer-specific survival (P<0.01). In Caki-2 cells, MMP-9-NF-κB PIP significantly reduced the expression levels of MMP-9 mRNA and inhibited cell invasion, but did not affect the cell proliferation activity. On the other hand, no effect was found in MMP-9-AP-1 PIP on MMP-9 mRNA expression, cell proliferation and invasion. We confirmed the inhibitory effects of MMP-9-NF-κB PIP on the expression of MMP-9 and subsequent invasion of Caki-2 cells. Since it was clearly shown that high MMP-9 expression levels were associated with poor prognosis of RCC, MMP-9 is a potential candidate target for RCC treatment. Transcription therapy using a minor groove binder, such as NF-κB PIP, may be a potential therapeutic agent for RCC, although further investigation is required.
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November 2013
Volume 43 Issue 5

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

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APA
Sato, A., Nagase, H., Obinata, D., Fujiwara, K., Fukuda, N., Soma, M. ... Takahashi, S. (2013). Inhibition of MMP-9 using a pyrrole-imidazole polyamide reduces cell invasion in renal cell carcinoma. International Journal of Oncology, 43, 1441-1446. https://doi.org/10.3892/ijo.2013.2073
MLA
Sato, A., Nagase, H., Obinata, D., Fujiwara, K., Fukuda, N., Soma, M., Yamaguchi, K., Kawata, N., Takahashi, S."Inhibition of MMP-9 using a pyrrole-imidazole polyamide reduces cell invasion in renal cell carcinoma". International Journal of Oncology 43.5 (2013): 1441-1446.
Chicago
Sato, A., Nagase, H., Obinata, D., Fujiwara, K., Fukuda, N., Soma, M., Yamaguchi, K., Kawata, N., Takahashi, S."Inhibition of MMP-9 using a pyrrole-imidazole polyamide reduces cell invasion in renal cell carcinoma". International Journal of Oncology 43, no. 5 (2013): 1441-1446. https://doi.org/10.3892/ijo.2013.2073