Mechanism of acquiring angiogenesis apoptosis in urogenital cancer

泌尿生殖癌获得血管生成凋亡的机制

• 批准号: 12470334
• 负责人: TSUKAMOTO Taiji
• 金额: $ 9.09万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470334/
• 关键词: RCC; Genestein; VEGF; PPARγ; PPAR γ; 15d-PG2; ピオグリタゾン; 血管新生; bFGF; アポトーシス; 前立腺癌; LBP-Tag; トランスジェニックマウス; 神経内分泌細胞癌アログラフト; ゲニステイン; PPAPγ

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.

1)染料木素是大豆中的异黄酮，具有酪氨酸激酶抑制活性，在体外抑制人肾细胞癌（RCC）细胞株血管内皮生长因子（VEGF） mRNA和碱性成纤维细胞生长因子（bFGF） mRNA的表达，在体内抑制血管生成。染料木素对RCC细胞系细胞生长的抑制作用呈剂量依赖性。这些发现表明染料木素具有多种抗肿瘤功能，提示它可能是一种新的治疗RCC的药物。2) c-src基因突变导致c-src酪氨酸激酶活性升高，可能导致RCC中VEGF过表达，影响细胞存活。为了验证假设，我们检测了RCC细胞系中的c-src突变。在所有细胞系中均未检测到突变，提示c-src基因突变似乎与这些事件无关。3)过氧化物酶体增殖物激活受体γ (PPAR γ)在RCC细胞株中表达。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。抑制细胞生长，诱导细胞凋亡。这些发现表明吡格列酮可能具有多种抗肿瘤功能，可用于治疗RCC患者。

项目成果

塚本泰司, 高橋 敦, 北村 寛: "腎細胞癌の診断と治療-最近の進歩"日本腎臓学会誌. 44. 779-785 (2002)

Yasushi Tsukamoto、Atsushi Takahashi、Hiroshi Kitamura：“肾细胞癌的诊断和治疗 - 最新进展”日本肾脏病学会杂志 44. 779-785 (2002)。

Kobayashi K, Sato T, Sunaoshi K, Takahashi a, Tamakawa M: "Spontaneous regression of primary renal cell carcinoma with inferior vena caval tumor thrombus"J.Urol.. 167. 242-243 (2002)

Kobayashi K、Sato T、Sunaoshi K、Takahashi a、Tamakawa M：“原发性肾细胞癌伴下腔静脉癌栓的自发消退”J.Urol.. 167. 242-243 (2002)

Oda T, Miyao N, Takahashi A, Masumori N, Itoh N, Tamakawa M, Tsukamoto T: "Growth rates of primary and metastatic lesions of renal cell carcinoma"Inteternational Journal of Urology. 8. 473-477 (2001)

Oda T、Miyao N、Takahashi A、Masumori N、Itoh N、Tamakawa M、Tsukamoto T：“肾细胞癌原发性和转移性病变的生长率”国际泌尿外科杂志。

Tsukamoto T, Takahashi A, Kitamura H: "Recent progress in diagnosis and treatment of renal cell carcinoma"Jpn.J.Nephrol.. 44. 779-785 (2002)

Tsukamoto T、Takahashi A、Kitamura H：“肾细胞癌诊断和治疗的最新进展”Jpn.J.Nephrol.. 44. 779-785 (2002)

Oda T, Takahashi A, Miyao N, Yanase M, Masumoti N, et al.: "Cell proliferation, apoptosis, angiogenesis and growth rate of incidentally founf cell carcinoma"International Journal of Urology. 10. 13-18 (2003)

Oda T、Takahashi A、Miyao N、Yanase M、Masumoti N 等人：“偶然发现的细胞癌的细胞增殖、凋亡、血管生成和生长速率”国际泌尿学杂志。