Related Experiment Video
Updated: Aug 22, 2026

TRUE Gene Silencing: Screening of a Heptamer-type Small Guide RNA Library for Potential Cancer Therapeutic Agents
Published on: June 2, 2016
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.
Objective:
RNA interference (RNAi), mediated by small interfering RNA (siRNA), silences genes with a high degree of specificity and potentially represents a general approach for molecularly targeted anticancer therapy. The aim of this study was to evaluate the ability of systemically administered siRNA to silence gene expression in vivo and to assess the effect of this approach on tumor growth using a murine pancreatic adenocarcinoma xenograft model.
Summary Background Data:
Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is widely overexpressed in human gastrointestinal cancer. Overexpression of CEACAM6 promotes cell survival under anchorage independent conditions, a characteristic associated with tumorigenesis and metastasis.
Methods:
CEACAM6 expression was quantified by real-time polymerase chain reaction (PCR) and Western blot. Mice (n = 10/group) were subcutaneously xenografted with 2 x 10 BxPC3 cells (which inherently overexpress CEACAM6). Tumor growth, CEACAM6 expression, cellular proliferation (Ki-67 immunohistochemistry), apoptosis, angiogenesis (CD34 immunohistochemistry), and survival were compared for mice administered either systemic CEACAM6-specific or control single-base mismatch siRNA over 6 weeks, following orthotopic tumor implantation.
Results:
Treatment with CEACAM6-specific siRNA suppressed primary tumor growth by 68% versus control siRNA (P < 0.05) and was associated with a decreased proliferating cell index, impaired angiogenesis and increased apoptosis in the xenografted tumors. CEACAM6-specific siRNA completely inhibited metastasis (0% of mice versus 60%, P < 0.05) and significantly improved survival, without apparent toxicity.
Conclusions:
Our data demonstrate the efficacy of systemically administered siRNA as a therapeutic modality in experimental pancreatic cancer. This novel therapeutic strategy may be applicable to a broad range of cancers and warrants investigation in patients with refractory disease.
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.
Related Concept Videos
siRNA - Small Interfering RNAs
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
Experimental RNAi
RNA Interference
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
RNA Interference
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
Targeted Cancer Therapies
There are several types of targeted therapies against specific...
Targeted Cancer Therapies
There are several types of targeted therapies against specific...

