Systemic siRNA-mediated gene silencing: a new approach to targeted therapy of cancer

Mark S Duxbury1, Evan Matros, Hiromichi Ito

  • 1Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Annals of Surgery
|September 24, 2004
PubMed
Abstract

Insights

Systemic RNA interference (siRNA) therapy effectively suppressed pancreatic cancer growth and metastasis in mice by targeting CEACAM6. This approach offers a promising, non-toxic treatment strategy for refractory cancers.

Area of Science:

  • Molecular biology
  • Oncology
  • Gene silencing therapeutics

Background:

  • Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is overexpressed in gastrointestinal cancers.
  • CEACAM6 overexpression promotes cancer cell survival and metastasis.

Purpose of the Study:

  • To evaluate systemic small interfering RNA (siRNA) for gene silencing in vivo.
  • To assess the therapeutic effect of siRNA on pancreatic cancer growth in a murine xenograft model.

Main Methods:

  • Mice xenografted with pancreatic cancer cells were treated with CEACAM6-specific or control siRNA.
  • Tumor growth, CEACAM6 expression, proliferation, apoptosis, and angiogenesis were analyzed.

Main Results:

  • CEACAM6-specific siRNA significantly suppressed tumor growth (68%) and inhibited metastasis (0% vs 60%).
  • Treatment reduced proliferation, impaired angiogenesis, and increased apoptosis.
  • Improved survival was observed without apparent toxicity.

Conclusions:

  • Systemically administered siRNA is effective for experimental pancreatic cancer treatment.
  • This RNA interference approach shows potential for treating various refractory cancers.

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