Mechanism of acquiring angiogenesis apoptosis in urogenital cancer

1)染料木黄酮（Genistein）是大豆中的一种黄酮类化合物，具有酪氨酸激酶抑制活性，在体外可抑制人肾细胞癌（RCC）细胞系中血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）mRNA的表达，在体内可抑制血管生成。此外，染料木黄酮抑制肾癌细胞株的细胞生长，并呈剂量依赖性。这些结果表明，染料木黄酮具有多种抗肿瘤作用，有望成为治疗肾细胞癌的新药物。2）c-src基因突变引起的c-src酪氨酸激酶活性升高可能导致肾细胞癌中VEGF的过度表达和细胞存活。为了验证假设，我们检测了RCC细胞系中的c-src突变。所有细胞系均未检测到c-src基因突变，提示c-src基因突变可能不参与这些事件的发生。3）过氧化物酶体增殖物激活受体γ（PPAR γ）在所检测的肾癌细胞系中表达。PPAR γ配体吡格列酮是一种用于治疗2型糖尿病的药物，可抑制RCC细胞中VEGF和bFGF的表达和产生。此外，它还能抑制细胞生长，诱导细胞凋亡。这些结果表明吡格列酮可能通过多种抗肿瘤作用治疗RCC患者。

1) Genistein which is an isoflavone in soy beans and has inhibitory activity of tyrosine kinase, suppressed both vascular endothelial growth factor (VEGF) mRNA and basic fibroblast growth factor (bFGF) mRNA expression in human renal cell carcinoma (RCC) cell lines in vitro, and inhibited in vivo angiogenesis. Furthermore, genistein inhibited the cell growth in RCC cell line in a dose-dependent manner. These findings show that genistein has multiple antitumor functions, suggesting that it may be a novel therapeutic agent for RCC patients.2) Elevated levels of c-src tyrosine kinase activity due to mutation of c-src genemay result in overexpression of VEGF and cell survival in RCC. To test hypothesis, we examined c-src mutation in RCC cell lines. No mutation was detected in all cell lines, suggesting that mutation of c-src gene dose not seem to be involved in these events.3) Peroxisome proliferator-activated receptor gamma (PPAR γ) was expressed in RCC cell lines examined. PPAR γ ligand pioglitazone, a agent used in the treatment of type2 diabetes, inhibited VEGF and bFGF expression and production in RCC cells. Furthermore, it inhibited the cell growth and induced apoptosis. These findings indicate that pioglitazone may be useful in treatment RCC patients by multiple antitumor functions.