Advertisement

Interactions between Anti-Inflammatory Drugs and Cancer Chemotherapy

  • A. Bennett
  • J. D. Gaffen
Part of the NATO ASI Series book series (NSSA, volume 177)

Abstract

As a result of experiments indicating relationships of prostaglandins (PGs) to human mammary cancer (Bennett et al, 1977), we studied the effects of PG synthesis inhibitors on murine NC transplanted carcinomas in vivo and in vitro. Flurbiprofen or indomethacin (INDO) prolonged the survival of the host mice (Bennett et al, 1979, 1982), and potentiated the effect of the combined cytotoxic drug regimen of methotrexate (MTX) plus melphalan (MEL) (Berstock et al, 1979; Bennett et al, 1982; Berstock et al, 1982). This drug combination was used in the same ratio as in a human breast cancer study then being carried out by another group in our Department. However, we later found that the beneficial interaction with INDO on the NC tumour in vivo also occurs with just MTX alone (Bennett et al, 1987). Other experiments described below using cell culture support this finding.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bennett, A., Charl i er, E.M., McDonald, A.M., Simpson, J.S., Stamford, I.F. and Zebro, T. (1977). Prostaglandins and breast cancer. Lancet ii, 624¬626.Google Scholar
  2. Bennett, A., Houghton, J., Leaper, D.S. and Stamford, I.F. (1979). Cancer growth, response to treatment and survival time in mice: Beneficial effect of the prostaglandin synthesis inhibitor flurbiprofen. Prostaglandins, 17, 179–191.Google Scholar
  3. Bennett, A., Berstock, D.A. and Carroll, M.A. (1982). Increased survival of cancer-bearing mice treated with inhibitors of prostaglandin synthesis alone or with chemotherapy. Br. J. Cancer, 45, 762–768.Google Scholar
  4. Bennett, A., Gaffen, J.D., Melhuish, P.B. and Stamford, I.F. (1987). Studies on the mechanism by which indomethacin increases the anticancer effect of methotrexate. Br. J. Pharmacol, 91: 229–235.Google Scholar
  5. Bennett A., Gaffen J.D. and Chambers, E. (1988). Cyclo-oxygenase inhibitors and cell killing by cytotoxic drugs. In: Proceedings of the Taipei Conference on Prostaglandin and Leukotriene Research, in press.Google Scholar
  6. Berstock, D.A., Houghton, J. and Bennett, A. (1979). Improved anticancer effect by combining cytotoxic drugs with an inhibitor of prostaglandin synthesis. Cancer Treat. Rev. 6 (Suppl), 69–71.Google Scholar
  7. Berstock, D.A., Carroll, M.A. and Bennett, A. (1982). Murine cancer: the interaction of flurbiprofen with high-dose chemotherapy. 5th International Conference on Prostaglandins, abstract 149.Google Scholar
  8. Gaffen, J.D., Bennett, A, Barer, M.R. (1985). A new method for studying cell growth in suspension, and its use to show that indomethacin enhances cell killing by methotrexate. J. Pharm, Pharmacol., 37, 261–263.Google Scholar
  9. Gaffen, J.D., Tsang, R. and Bennett, A. (1986). Increased killing of malignant cells by giving indomethacin with methotrexate. Prog. Lipid. Res., 25, 543–545.Google Scholar
  10. Henderson, G.B., Zevely, E.M. and Huennekens, F.M. (1978). Cylic adenosine 3’:5’-monophosphate and methotrexate transport in L1210 cells. Cancer Res., 38, 859–861.PubMedGoogle Scholar
  11. Hewitt, H.B., Blake, E.R. and Wal der, A.S. (1976). A critique of the evidence for active host defence against cancer, based on personal studies of 27 murine tumours of spontaneous origin. Br. J. Cancer, 33, 241–259.Google Scholar
  12. Langlois, A.J., Holder Jr., W.D., Iglehart, J.D., Nelson-Rees, W.A., Wells Jr, S.A. and Bolognesi, D.P. (1979). Morpholigical and biochemical properties of a new human breast cancer cell line. Cancer Res., 39, 2604¬2613.Google Scholar
  13. Zor, U., Her, E., Talmon, J., Kohen, F., Harell, T., Moshonov, S. and Rivnay, B. (1987). Hydrocortisone inhibits antigen-induced rise in intracellular free calcium concentration and abolishes leukotriene C4 production in leukemic basophils. Prostaglandins 34, 29–40.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • A. Bennett
    • 1
  • J. D. Gaffen
    • 1
  1. 1.Department of SurgeryKing’s College School of Medicine and Dentistry The Rayne InstituteLondonEngland

Personalised recommendations