Mechanism of acquiring angiogenesis apoptosis in urogenital cancer

1)金雀异黄素是大豆中的一种异黄酮类化合物，具有酪氨酸激酶抑制活性，在体外可抑制人肾癌细胞系血管内皮生长因子和碱性成纤维细胞生长因子的mRNA表达，并抑制体内血管生成。金雀异黄素对肾癌细胞生长的抑制作用呈剂量依赖关系。这些发现表明金雀异黄素具有多种抗肿瘤功能，提示它可能是一种新的治疗肾癌的药物。2)c-src基因突变导致的c-src酪氨酸激酶活性升高可能导致血管内皮生长因子的过度表达和肾癌细胞的存活。为了验证假设，我们研究了肾癌细胞系中的c-src突变。在所有细胞系中均未检测到突变，提示c-src基因突变可能与上述事件无关。3)肾细胞癌细胞株表达过氧物酶增殖物激活受体γ。治疗2型糖尿病的药物吡格列酮可抑制肾癌细胞γ和bFGFmRNA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肾癌患者。

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.