Effects of tamoxifen and interferon-beta or the combination on tumor-induced angiogenesis

D J Lindner1, E C Borden

  • 1Department of Microbiology and Immunology, Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD, USA.

Insights

Tamoxifen and interferon-beta (IFN-beta) inhibit tumor growth by reducing blood vessel formation (angiogenesis). Combination therapy completely prevented tumor growth in mice, showing additive anti-angiogenic effects.

Area of Science:

  • Oncology
  • Cancer Biology
  • Pharmacology

Background:

  • Anti-tumor agents can inhibit tumor growth by targeting angiogenesis.
  • Tamoxifen and interferon-alpha/beta (IFN-alpha/beta) show combined anti-proliferative effects.
  • Host-mediated effects, including angiogenesis modulation, are crucial for in vivo tumor growth inhibition.

Purpose of the Study:

  • To assess the anti-angiogenic and anti-tumor effects of tamoxifen and IFN-beta on human breast and ovarian carcinoma xenografts.
  • To evaluate the combined efficacy of tamoxifen and IFN-beta in inhibiting tumor growth and angiogenesis.
  • To determine if anti-angiogenic effects precede measurable tumor volume reduction.

Main Methods:

  • Treatment of nude mice bearing MCF-7 (breast) and NIH-OVCAR-3 (ovarian) carcinoma xenografts with tamoxifen and/or IFN-beta.
  • Quantification of tumor vascularity by counting vessels at the tumor periphery.
  • Measurement of tumor growth inhibition over a ten-week treatment period.

Main Results:

  • Tamoxifen and IFN-beta significantly reduced tumor angiogenesis in both xenograft models, with greater effects on NIH-OVCAR-3 tumors.
  • Combination treatment demonstrated additive anti-angiogenic effects.
  • Both agents inhibited xenograft tumor growth as single agents, and their combination completely prevented tumor growth.
  • Inhibition of angiogenesis was observed before significant changes in tumor volume.

Conclusions:

  • Tamoxifen and IFN-beta exhibit potent anti-angiogenic and anti-tumor activities against both estradiol-dependent and independent human carcinomas in vivo.
  • The combination therapy of tamoxifen and IFN-beta leads to complete tumor growth prevention.
  • Additive anti-angiogenic effects, potentially mediated by enhanced IFN-induced gene expression, contribute to the overall anti-tumor efficacy.

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