Inhibitory effect on expression of angiogenic factors by antiangiogenic agents in renal cell carcinoma.
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.
Sasamura
H
H
Department of Urology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan.
Takahashi
A
A
Miyao
N
N
Yanase
M
M
Masumori
N
N
Kitamura
H
H
Itoh
N
N
Tsukamoto
T
T
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis*; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D008222:Lymphokines / Q000096:biosynthesis*; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D019833:Genistein