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Cancer Chemotherapy and Pharmacology

, Volume 30, Issue 5, pp 377–384 | Cite as

Minocycline in combination with chemotherapy or radiation therapy in vitro and in vivo

  • Enrique Alvarez Sotomayor
  • Beverly A. Teicher
  • Gary N. Schwartz
  • Sylvia A. Holden
  • Krishna Menon
  • Terence S. Herman
  • Emil FreiIII
Original Articles Minocycline, Chemotherapy, Radiation Therapy

Summary

In the present study the potential of minocycline, a semisynthetic tetracycline that inhibits collagenase activity in vivo, as an adjuvant to standard anticancer therapies was explored in vitro and in vivo. In EMT-6 cells, minocycline proved to be only minimally cytotoxic, producing a 50% cell kill at concentrations of 132 and 220 μm in normally oxygenated and hypoxic cells, respectively, after 24 h exposure to the drug. In vitro, there appeared to be no interaction between minocycline and cisplatin (CDDP), melphalan, 4-hydroperoxycyclophosphamide, or radiation. In tumor-cell survival studies using the FSaIIC murine fibrosarcoma, short-term treatment with minocycline (5×5 mg/kg given over 24 h) was only minimally cytotoxic and did not alter the tumor response to a range of radiation doses. However, when minocycline (5×5 mg/kg given over 24 h) was added to treatment with cyclophosphamide, there was a 4-fold increase in FSaIIC tumor-cell killing across the dose range of cyclophosphamide doses tested, whereas the killing of bone marrow granulocyte macrophage colony-forming units (CFU-GM) remained unchanged. The Lewis lung carcinoma was used to assess the response of both the primary tumor and metastatic lung disease to treatment with minocycline (14×5 mg/kg) given alone or in combination with several cytotoxic anticancer drugs or with radiation delivered locally to the primary tumor. Of the various therapies tested, minocycline proved to be especially effective as an addition to treatment with cyclophosphamide both in increasing the response of the primary tumor and in reducing the number of lung metastases. The tumor growth delay produced by melphalan, radiation, Adriamycin, and bleomycin was also increased by the addition of minocycline to these therapies. These results indicate that minocycline given in clinically achievable doses may be an effective addition to some standard therapeutic regimens and that the mechanism of modulation by minocycline is likely to involve an effect of the drug on the host and not its direct interaction with other therapeutic modalities at the level of the tumor cell.

Keywords

Cyclophosphamide Bleomycin CDDP Adriamycin Minocycline 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Enrique Alvarez Sotomayor
    • 1
    • 2
  • Beverly A. Teicher
    • 1
    • 2
  • Gary N. Schwartz
    • 1
    • 2
  • Sylvia A. Holden
    • 1
    • 2
  • Krishna Menon
    • 1
    • 2
  • Terence S. Herman
    • 1
    • 2
  • Emil FreiIII
    • 1
    • 2
  1. 1.Dana-Farber Cancer InstituteBostonUSA
  2. 2.Joint Center for Radiation TherapyBostonUSA

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