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Updated: Jun 18, 2026

DNA Vector-based RNA Interference to Study Gene Function in Cancer
Published on: June 4, 2012
Targeting for insulin-like growth factor-I receptor with short hairpin RNA for human digestive/gastrointestinal
Yu Wang1, Yasushi Adachi, Arisa Imsumran
1First Department of Internal Medicine, Sapporo Medical University, W-16 Chuo-ku, Sapporo 060-8543, Japan.
Background And Aims:
Insulin-like growth factor (IGF)-I receptor (IGF-IR) signaling plays important parts in both the tumorigenicity and progression of digestive/gastrointestinal malignancies. In this study, we sought to test the effectiveness of a practical approach to blocking IGF-IR signaling using RNA interference delivered by recombinant adenoviruses.
Methods:
We constructed a recombinant adenovirus expressing short hairpin RNA targeting IGF-IR (shIGF-IR) and assessed its effect on signal transduction, proliferation, and survival in digestive/gastrointestinal cancer cell lines representing colorectal, gastric, and pancreatic adenocarcinoma, esophageal squamous cell carcinoma, and hepatoma. We analyzed the effects of shIGF-IR alone and with chemotherapy in vitro and in nude mouse xenografts, as well as on insulin signaling and hybrid receptor formation between IGF-IR and insulin receptor.
Results:
shIGF-IR blocked expression and autophosphorylation of IGF-IR and downstream signaling by the IGFs, but not by insulin. shIGF-IR suppressed proliferation and carcinogenicity in vitro and up-regulated apoptosis in a dose-dependent fashion. shIGF-IR augmented the effects of chemotherapy on in vitro growth and apoptosis induction. Moreover, the combination of shIGF-IR and chemotherapy was highly effective against tumors in mice. shIGF-IR reduced hybrid receptor formation without effect on expression of insulin receptor.
Conclusions:
shIGF-IR may have therapeutic utility in human digestive/gastrointestinal cancers, both alone and in combination with chemotherapy.
Insights
This study shows that short hairpin RNA targeting the insulin-like growth factor I receptor (shIGF-IR) effectively inhibits digestive/gastrointestinal cancer growth. Combining shIGF-IR with chemotherapy enhances treatment efficacy in preclinical models.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Insulin-like growth factor (IGF)-I receptor (IGF-IR) signaling is crucial for the development and progression of digestive/gastrointestinal cancers.
- Targeting IGF-IR offers a potential therapeutic strategy for these malignancies.
Purpose of the Study:
- To evaluate the efficacy of blocking IGF-IR signaling using RNA interference delivered by recombinant adenoviruses.
- To assess the therapeutic potential of short hairpin RNA targeting IGF-IR (shIGF-IR) in various digestive/gastrointestinal cancer models.
Main Methods:
- Constructed a recombinant adenovirus expressing shIGF-IR.
- Assessed the effects of shIGF-IR on signal transduction, proliferation, and apoptosis in colorectal, gastric, pancreatic, esophageal, and liver cancer cell lines.
- Evaluated shIGF-IR efficacy alone and with chemotherapy in vitro, in mouse xenografts, and on insulin signaling pathways.
Main Results:
- shIGF-IR effectively blocked IGF-IR expression and signaling without affecting insulin signaling.
- shIGF-IR suppressed cancer cell proliferation and carcinogenicity while inducing apoptosis in a dose-dependent manner.
- Combination therapy of shIGF-IR and chemotherapy demonstrated significant efficacy against tumors in vivo and enhanced apoptosis induction in vitro.
Conclusions:
- shIGF-IR shows promise as a therapeutic agent for digestive/gastrointestinal cancers.
- Combination of shIGF-IR with chemotherapy may represent a potent therapeutic strategy for treating these cancers.
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