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Enhanced inhibitory effect of the matrix metalloproteinase inhibitor Ro 28-2653 in combination with estramustine and etoposide on the prostate carcinoma in the rat Dunning orthotopic tumor model

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Abstract

Purpose: Therapeutic efficacy of the novel matrix metalloproteinase (MMP) inhibitor Ro 28-2653 has been shown in various models of different tumor entities. We hypothesized that the inhibitor effect of Ro 28-2653 on the tumor growth could be improved by combination with chemotherapeutic drugs and examined therefore the effect of Ro 28-2653 alone and in combination with etoposide or estramustine in the MatLyLu Dunning R-3327 rat tumor model characteristic for the androgen-independent prostate cancer (PCa). Methods: In vitro effects were estimated measuring the proliferation of MatLyLu cells incubated with the three agents alone or in combination using the XTT test. The in vivo effects of the agents alone or in combination were examined by measuring the tumor weight 18 days after tumor cell injection. Results: The proliferation rate was only inhibited by etoposide while that effect was increased in combination with Ro 28-2653 and estramustine. Ro 28-2653 reduced the tumor weight by 86%. That effect was significantly increased in combination with etoposide to 92%. Conclusions: The inhibitory effect of the MMP inhibitor Ro 28-2653 on the tumor growth in the Dunning PCa model is enhanced by the standard chemotherapeutic drug etoposide. A combined application of both agents could be considered as potential tool to improve the therapy of patients with advanced PCa after failure of hormonal treatment.

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Acknowledgments

The authors thank Sabine Becker, Silke Klotzek, and Ines Baumert for valuable technical assistance. We thank Roche Diagnostics GmbH, Pharma Research, Penzberg, Germany for providing Ro 28-2653. The study contains parts of the thesis of W.R.

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Authors and Affiliations

  1. Department of Urology, University Hospital Charité, Humboldt University, Schumannstraße 20/21, 10098, Berlin, Germany

    Claudia Abramjuk, Michael Lein, Winfried Rothaug, Stefan A. Loening & Klaus Jung

  2. Roche Diagnostics GmbH, Pharma Research, Penzberg, Germany

    Hans-Willi Krell

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  1. Claudia Abramjuk
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  2. Michael Lein
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  3. Winfried Rothaug
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  4. Hans-Willi Krell
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  5. Stefan A. Loening
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  6. Klaus Jung
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Correspondence to Klaus Jung.

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Abramjuk, C., Lein, M., Rothaug, W. et al. Enhanced inhibitory effect of the matrix metalloproteinase inhibitor Ro 28-2653 in combination with estramustine and etoposide on the prostate carcinoma in the rat Dunning orthotopic tumor model. Cancer Chemother Pharmacol 59, 275–282 (2007). https://doi.org/10.1007/s00280-006-0269-7

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  • DOI: https://doi.org/10.1007/s00280-006-0269-7

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