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Inhibitory effect on expression of angiogenic factors by antiangiogenic agents in renal cell carcinoma
H Sasamura1, A Takahashi, N Miyao
1Department of Urology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan.
Abstract:
Since it has been widely recognised that renal cell carcinoma is refractory to standard therapies such as chemotherapy and radiotherapy, a new modality of treatment is needed. One of the potential alternative therapies for renal cell carcinoma may be inhibition of angiogenesis. In this study, we analysed the inhibitory effects of several potential agents on expression of angiogenic factors such as vascular endothelial growth factor and basic fibroblast growth factor, which are the main mediators in angiogenesis of renal cell carcinoma. We used medroxyprogesterone acetate, interferon-alpha, interferon-gamma, minocycline hydrochrolide and genistein, which are known to be antiangiogeneic. Northern blot analyses revealed that, among the five agents examined, genistein had a strong inhibitory effect on expression of vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA. Medroxyprogesterone acetate and interferon-alpha did not significantly decrease the level of either vascular endothelial growth factor mRNA or basic fibroblast growth factor mRNA. Interferon-gamma and minocycline had mild inhibitory effects on vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA expression. Genistein also inhibited both vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA expression after treatment with epidermal growth factor and hypoxia. These findings suggest that one of the mechanisms of the inhibition of angiogenesis by genistein is suppression of the expression of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor in renal cell carcinoma.
Insights
Genistein effectively inhibits angiogenesis in renal cell carcinoma by suppressing key growth factors. This finding offers a promising new therapeutic avenue for this difficult-to-treat cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Renal cell carcinoma (RCC) often resists conventional treatments like chemotherapy and radiotherapy.
- Angiogenesis, the formation of new blood vessels, is crucial for RCC growth and is a potential therapeutic target.
- Identifying novel anti-angiogenic agents is essential for developing effective RCC therapies.
Purpose of the Study:
- To evaluate the anti-angiogenic potential of five agents: medroxyprogesterone acetate, interferon-alpha, interferon-gamma, minocycline hydrochloride, and genistein.
- To assess the inhibitory effects of these agents on the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in RCC.
- To investigate the mechanism by which genistein inhibits angiogenesis.
Main Methods:
- Northern blot analysis was employed to quantify mRNA expression levels of VEGF and bFGF.
- Five known anti-angiogenic agents were tested for their effects on VEGF and bFGF mRNA expression.
- The impact of genistein on VEGF and bFGF mRNA expression was further examined under conditions of epidermal growth factor stimulation and hypoxia.
Main Results:
- Genistein demonstrated a significant inhibitory effect on both VEGF and bFGF mRNA expression.
- Medroxyprogesterone acetate and interferon-alpha showed no significant impact on VEGF or bFGF mRNA levels.
- Interferon-gamma and minocycline exhibited mild inhibitory effects on VEGF and bFGF mRNA expression.
- Genistein suppressed VEGF and bFGF mRNA expression even when induced by epidermal growth factor and hypoxia.
Conclusions:
- Genistein is a potent inhibitor of angiogenesis in renal cell carcinoma.
- Suppression of vascular endothelial growth factor and basic fibroblast growth factor expression is a key mechanism underlying genistein's anti-angiogenic activity.
- Genistein represents a promising therapeutic candidate for renal cell carcinoma treatment.