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Updated: May 27, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Apigenin attenuates insulin-like growth factor-I signaling in an autochthonous mouse prostate cancer model
Sanjeev Shukla1, Gregory T MacLennan, Pingfu Fu
1Department of Urology, Case Western Reserve University, 2109 Adelbert Road, Wood Research Tower, RTG01, Cleveland, Ohio 44106, USA.
Purpose:
Deregulation of IGF signaling plays an important role in prostate cancer and contributes to invasion and metastasis. We determined the effect of apigenin, a plant flavone, on IGF signaling and its downstream targets in TRAMP mice.
Methods:
Mice received p.o. apigenin at 20 and 50 μg/day dose for 20 weeks. ELISA, Western blotting and immunohistochemistry were performed to examine the IGF-axis and its regulated pathway in response to apigenin intake.
Results:
Increased serum levels of IGF-I, VEGF, uPA and concomitant decrease in IGFBP-3 were observed; p-Akt (Ser473), p-ERK1 (T202/Y204) and p-ERK2 (T185/Y187) expression increased in the dorso-lateral prostate of TRAMP mice during the course of cancer progression as a function of age. P.o. administration of apigenin resulted in substantial reduction in the levels of IGF-I and increase in the levels of IGFBP-3 in the serum and the dorso-lateral prostate. This modulation of IGF/IGFBP-3 was associated with an inhibition of p-Akt and p-ERK1/2. Apigenin intake resulted in marked inhibition of VEGF, uPA, MMP-2 and MMP-9 which coincided with tumor growth inhibition and complete absence of metastasis in TRAMP mice.
Conclusions:
Our results indicate that apigenin effectively suppressed prostate cancer progression in TRAMP mice by attenuating IGF-I/IGFBP-3 signaling and inhibiting angiogenesis and metastasis.
Insights
Apigenin, a plant flavone, suppressed prostate cancer progression in TRAMP mice. It attenuated insulin-like growth factor (IGF)-I/IGF binding protein-3 signaling, inhibiting angiogenesis and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Insulin-like growth factor (IGF) signaling deregulation is crucial in prostate cancer, driving invasion and metastasis.
- Apigenin, a naturally occurring plant flavone, has potential anti-cancer properties.
Purpose of the Study:
- To investigate the effect of apigenin on IGF signaling and its downstream targets in TRAMP mice, a model for prostate cancer.
- To determine if apigenin can inhibit prostate cancer progression, angiogenesis, and metastasis.
Main Methods:
- TRAMP mice were administered apigenin orally at doses of 20 and 50 μg/day for 20 weeks.
- Enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry were used to analyze IGF-axis components and signaling pathways.
Main Results:
- Apigenin administration significantly reduced serum and prostate levels of IGF-I and increased IGFBP-3.
- This was associated with decreased phosphorylation of Akt and ERK1/2 signaling pathways.
- Apigenin markedly inhibited VEGF, uPA, MMP-2, and MMP-9, leading to reduced tumor growth and complete absence of metastasis.
Conclusions:
- Apigenin effectively suppressed prostate cancer progression in TRAMP mice.
- The mechanism involves the attenuation of IGF-I/IGFBP-3 signaling, inhibition of angiogenesis, and prevention of metastasis.
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